Thin-walled scaffolds having modified marker structure near distal end

ABSTRACT

A thin-walled scaffold includes a radiopaque marker connected to a link. In a first example, the marker is retained on the strut by a head at one or both ends by swaging. In a second example of a thin-walled scaffold the link is modified to avoid interference during crimping. In a third example a distal end of the thin-walled scaffold is modified to improve deliverability of the thin-walled scaffold. These features are combined in a fourth example.

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention relates to bioresorbable scaffolds; moreparticularly, this invention relates to bioresorbable scaffolds fortreating an anatomical lumen of the body.

Description of the State of the Art

Radially expandable endoprostheses are artificial devices adapted to beimplanted in an anatomical lumen. An “anatomical lumen” refers to acavity, or duct, of a tubular organ such as a blood vessel, urinarytract, and bile duct. Stents are examples of endoprostheses that aregenerally cylindrical in shape and function to hold open and sometimesexpand a segment of an anatomical lumen. Stents are often used in thetreatment of atherosclerotic stenosis in blood vessels. “Stenosis”refers to a narrowing or constriction of the diameter of a bodilypassage or orifice. In such treatments, stents reinforce the walls ofthe blood vessel and prevent restenosis following angioplasty in thevascular system. “Restenosis” refers to the reoccurrence of stenosis ina blood vessel or heart valve after it has been treated (as by balloonangioplasty, stenting, or valvuloplasty) with apparent success.

The treatment of a diseased site or lesion with a stent involves bothdelivery and deployment of the stent. “Delivery” refers to introducingand transporting the stent through an anatomical lumen to a desiredtreatment site, such as a lesion. “Deployment” corresponds to expansionof the stent within the lumen at the treatment region. Delivery anddeployment of a stent are accomplished by positioning the stent aboutone end of a catheter, inserting the end of the catheter through theskin into the anatomical lumen, advancing the catheter in the anatomicallumen to a desired treatment location, expanding the stent at thetreatment location, and removing the catheter from the lumen.

Scaffolds and stents traditionally fall into two generalcategories—balloon expanded and self-expanding. The later type expands(at least partially) to a deployed or expanded state within a vesselwhen a radial restraint is removed, while the former relies on anexternally-applied force to configure it from a crimped or stowed stateto the deployed or expanded state.

Self-expanding stents are designed to expand significantly when a radialrestraint is removed such that a balloon is often not needed to deploythe stent. Self-expanding stents do not undergo, or undergo relativelyno plastic or inelastic deformation when stowed in a sheath or expandedwithin a lumen (with or without an assisting balloon). Balloon expandedstents or scaffolds, by contrast, undergo a significant plastic orinelastic deformation when both crimped and later deployed by a balloon.

In the case of a balloon expandable stent, the stent is mounted about aballoon portion of a balloon catheter. The stent is compressed orcrimped onto the balloon. Crimping may be achieved by use of aniris-type or other form of crimper, such as the crimping machinedisclosed and illustrated in US 2012/0042501. A significant amount ofplastic or inelastic deformation occurs both when the balloon expandablestent or scaffold is crimped and later deployed by a balloon. At thetreatment site within the lumen, the stent is expanded by inflating theballoon.

The stent must be able to satisfy a number of basic, functionalrequirements. The stent (or scaffold) must be capable of sustainingradial compressive forces as it supports walls of a vessel. Therefore, astent must possess adequate radial strength. After deployment, the stentmust adequately maintain its size and shape throughout its service lifedespite the various forces that may come to bear on it. In particular,the stent must adequately maintain a vessel at a prescribed diameter fora desired treatment time despite these forces. The treatment time maycorrespond to the time required for the vessel walls to remodel, afterwhich the stent is no longer needed.

Examples of bioresorbable polymer scaffolds include those described inU.S. Pat. No. 8,002,817 to Limon, U.S. Pat. No. 8,303,644 to Lord, andU.S. Pat. No. 8,388,673 to Yang. FIG. 1 shows a distal region of abioresorbable polymer scaffold designed for delivery through anatomicallumen using a catheter and plastically expanded using a balloon. Thescaffold has a cylindrical shape having a central axis 2 and includes apattern of interconnecting structural elements, which will be called bararms or struts 4. Axis 2 extends through the center of the cylindricalshape formed by the struts 4. The stresses involved during compressionand deployment are generally distributed throughout the struts 4 but arefocused at the bending elements, crowns or strut junctions. Struts 4include a series of ring struts 6 that are connected to each other atcrowns 8. Ring struts 6 and crowns 8 form sinusoidal rings 5. Rings 5are arranged longitudinally and centered on an axis 2. Struts 4 alsoinclude link struts 9 that connect rings 5 to each other. Rings 5 andlink struts 9 collectively form a tubular scaffold 10 having axis 2represent a bore or longitudinal axis of the scaffold 10. Ring 5 d islocated at a distal end of the scaffold. Crown 8 form smaller angleswhen the scaffold 10 is crimped to a balloon and larger angles whenplastically expanded by the balloon. After deployment, the scaffold issubjected to static and cyclic compressive loads from surroundingtissue. Rings 5 are configured to maintain the scaffold's radiallyexpanded state after deployment.

Scaffolds may be made from a biodegradable, bioabsorbable,bioresorbable, or bioerodable polymer. The terms biodegradable,bioabsorbable, bioresorbable, biosoluble or bioerodable refer to theproperty of a material or stent to degrade, absorb, resorb, or erodeaway from an implant site. Scaffolds may also be constructed ofbioerodible metals and alloys. The scaffold, as opposed to a durablemetal stent, is intended to remain in the body for only a limited periodof time. In many treatment applications, the presence of a stent in abody may be necessary for a limited period of time until its intendedfunction of, for example, maintaining vascular patency and/or drugdelivery is accomplished. Moreover, it has been shown that biodegradablescaffolds allow for improved healing of the anatomical lumen as comparedto metal stents, which may lead to a reduced incidence of late stagethrombosis. In these cases, there is a desire to treat a vessel using apolymer scaffold, in particular a bioabsorable or bioresorbable polymerscaffold, as opposed to a metal stent, so that the prosthesis's presencein the vessel is temporary.

Polymeric materials considered for use as a polymeric scaffold, e.g.poly(L-lactide) (“PLLA”), poly(D,L-lactide-co-glycolide) (“PLGA”),poly(D-lactide-co-glycolide) or poly(L-lactide-co-D-lactide)(“PLLA-co-PDLA”) with less than 10% D-lactide,poly(L-lactide-co-caprolactone), poly(caprolactone), PLLD/PDLA stereocomplex, and blends of the aforementioned polymers may be described,through comparison with a metallic material used to form a stent, insome of the following ways. Polymeric materials typically possess alower strength to volume ratio compared to metals, which means morematerial is needed to provide an equivalent mechanical property.Therefore, struts must be made thicker and wider to have the requiredstrength for a stent to support lumen walls at a desired radius. Thescaffold made from such polymers also tends to be brittle or havelimited fracture toughness. The anisotropic and rate-dependent inelasticproperties (i.e., strength/stiffness of the material varies dependingupon the rate at which the material is deformed, in addition to thetemperature, degree of hydration, thermal history) inherent in thematerial, only compound this complexity in working with a polymer,particularly, bioresorbable polymers such as PLLA or PLGA.

An additional challenge with using a bioresorbable polymer (and polymersgenerally composed of carbon, hydrogen, oxygen, and nitrogen) for ascaffold structure is that the material is radiolucent with noradiopacity. Bioresorbable polymers tend to have x-ray absorptionsimilar to body tissue. A known way to address the problem is to attachradiopaque markers to structural elements of the scaffold, such as astrut, bar arm or link. For example, FIG. 1 shows a link element 9 dconnecting a distal end ring 5 d to an adjacent ring 5. The link element9 d has a pair of holes. Each of the holes holds a radiopaque marker 11.There are challenges to the use of the markers 11 with the scaffold 10.There needs to be a reliable way of attaching the markers 11 to the linkelement 9 d so that the markers 11 will not separate from the scaffoldduring a processing step like crimping the scaffold to a balloon or whenthe scaffold is balloon-expanded from the crimped state. These twoevents—crimping and balloon expansion—are particularly problematic formarker adherence to the scaffold because both events induce significantplastic deformation in the scaffold body. If this deformation causessignificant out of plane or irregular deformation of struts supporting,or near to markers the marker can dislodge (e.g., if the strut holdingthe marker is twisted or bent during crimping the marker can fall out ofits hole). A scaffold with radiopaque markers and methods for attachingthe marker to a scaffold body is discussed in US20070156230.

There is a need to improve upon the reliability of radiopaque markersecurement to a scaffold for a thin-walled scaffold. Related to thisneed, there is a need to improve upon the performance characteristics ofa scaffold, especially thin-walled scaffolds made from a bioresorbablematerial that must be navigated around tortuous anatomy.

SUMMARY OF THE INVENTION

What is disclosed are bioresorbable scaffolds having radiopaque markersand scaffold structure holding such radiopaque material and enabling areduced a crimped profile ability and/or improved conformability to thecatheter when the catheter, upon which the scaffold is mounted, ispushed through tortuous anatomy.

Scaffolds disclosed herein are suited to meet one of, or a combinationof, the following objectives:

-   -   (i.) reduced crimped profile for a thin-walled scaffold carrying        a radiopaque marker,    -   (ii.) securing the marker to the thin-walled scaffold,    -   (iii.) reducing strain energy buildup in marker-holding        structure when the thin-walled scaffold is being deformed during        crimping, balloon expansion at a target vessel site, or delivery        of the scaffold to a target site, and    -   (iv.) reduced end ring flaring at a distal end of a scaffold for        a thin-walled scaffold or scaffold comprising PLLA and having a        wall thickness greater than 125 microns.

Being thin-walled, there has been realized through testing a need tomodify certain critical areas of the scaffold that had not previouslyposed problems when a higher wall thickness was used. An example of ascaffold having a higher wall thickness of 158 microns is described inUS 2010/0004735. It has been found that when a significant reduction inwall thickness is made, verses pre-existing bioresorbable scaffolds(e.g., from 160 microns wall thickness to 100 microns wall thickness)the arrangement, shape and dimensions of rings and link elements are,particularly at the distal end of the scaffold, in need of improvement.

A thin-walled scaffold is sought out because there is a clinical need tomaintain low profiles for struts exposed in the bloodstream. Bloodcompatibility, also known as hemocompatibility or thromboresistance, isa desired property for scaffolds and stents. The adverse event ofscaffold thrombosis, while a very low frequency event, carries with it ahigh incidence of morbidity and mortality. To mitigate the risk ofthrombosis, dual anti-platelet therapy is administered with all coronaryscaffold and stent implantation. This is to reduce thrombus formationdue to the procedure, vessel injury, and the implant itself. Scaffoldsand stents are foreign bodies and they all have some degree ofthrombogenicity. The thrombogenicity of a scaffold refers to itspropensity to form thrombus and this is due to several factors,including strut thickness, strut width, strut shape, total scaffoldsurface area, scaffold pattern, scaffold length, scaffold diameter,surface roughness and surface chemistry. Some of these factors areinterrelated. Low strut profile also leads to less neointimalproliferation as the neointima will proliferate to the degree necessaryto cover the strut. As such coverage is a necessary step to completehealing. Thinner struts are believed to endothelialize and heal morerapidly.

According to the various aspects of the invention, there is athin-walled scaffold (“scaffold”), medical device, method for makingsuch a scaffold, method of making a marker, attaching a marker to astrut, link or bar arm of a scaffold, method for crimping, or method forassembly of a medical device comprising such a scaffold having one ormore, or any combination of the following things (1) through (15):

-   -   (1) the scaffold crimped to a theoretical minimum crimp diameter        (D-min);    -   (2) the scaffold wall thickness is less than 125 microns, less        than 100 microns, about 100 microns or about 93 microns;    -   (3) a wavelength of a ring connected to a marker link is greater        than a wavelength of another ring not connected to the marker        link, and/or the wavelength of the ring connected to the marker        length has a different length wavelengths;    -   (4) a distance form a W crown to an adjacent U crown is higher        than a distance from a Y crown to an adjacent U crown;    -   (5) the scaffold is made from a tube comprising poly(L-lactide);    -   (6) the scaffold crimped to a balloon, wherein the scaffold        comprises a crimped state as shown and described in connection        with FIG. 4D, 6A or 7A;    -   (7) a method of crimping any of the scaffolds described in        connection with FIG. 3, 4, 5, 6, or 7;    -   (8) a method for attaching a radiopaque marker to the scaffold;    -   (9) a marker link having the dimensions shown and described in        connection with FIG. 2C.    -   (10) a ring has n crests where n is more than 5, or more than 6        and less than or equal to 12.    -   (11) the ring has 2 wavelengths of a first size and n−3        wavelengths of a second size, the first size being greater than        the second size;    -   (12) a ring connected to a marker link at a w crown has a first        width and the adjoined ring connected to the marker link has a        second width, greater than the first width;    -   (13) a ring connected to a marker link at a W crown has a wider        flat portion or than a Y crown flat portion connected to the        marker link and adjoined to the first ring.    -   (14) a first distance between rings adjoined by a marker link is        greater than a second distance between rings not joined by        marker links; and    -   (15) a first distance between rings adjoined by a non-linear        link marker link is greater than a second distance between rings        not joined by the non-linear marker link.    -   (16) D-min is about 1 mm or less than 1 mm    -   (17) An aspect ratio (AR) of the marker link for a thin-walled        scaffold is between about 4 and 5, or about 4.5, where AR is        defined as the maximum width of the marker link divided by the        wall thickness at the marker link.    -   (18) A first wavelength or ½ wavelength of a first ring is        greater than a second wavelength or ½ wavelength of an adjoined        second ring.    -   (19) A first wavelength or ½ wavelength between two crests of a        ring are different from a second wavelength between two other        crests of the same ring.    -   (20) A ring is sinusoidal or zig-zag.    -   (21) A half wavelength measured from a W crown formed between a        marker link and a first ring is about 15% higher than a half        wavelength measured from a Y crown formed between the marker        link and a second ring adjoined to the first ring; for a marker        link that has a maximum width about 200% higher than the maximum        width for a non-marker link.    -   (22) A wavelength measured from a W crown formed between a        marker link and a first ring is between about 5% and 10% higher        than the wavelength measured from a Y crown formed between the        marker link and a second ring adjoined to the first ring; for a        marker link that has a maximum width about 200% higher than the        maximum width for a non-marker link.    -   (23) A wavelength measured from a W crown/crest formed between a        marker link and a ring is between about 5% and 10% higher than        the wavelength measured between other crests of the ring; for a        marker link that has a maximum width about 200% higher than the        maximum width for a non-marker link.    -   (24) A crown with B1 that is greater than a crown width B2; for        example, a crown width B1 that is about 350% to about 400%        greater than a crown width B2;    -   (25) A ring spacing A12 between a first ring and a second ring        is greater than a ring spacing A23 between a second ring and a        third ring; for example A12 is about 40% greater than A23.    -   (26) A link is a straight link or a non-linear link; for example        link 20 and link 636.    -   (27) The length c1 that is about 36% higher than the length c2        for a marker link.    -   (28) The length c1 that is about 36% higher than the length c2        for a non-linear link.    -   (29) A medical device, comprising: a thin-walled scaffold having        a network of rings interconnected by links, wherein each ring        has a plurality of crests, wherein a crest is one of a U crown,        Y crown and a W crown, each ring extends circumferentially in an        undulating fashion along a vertical axis (B-B) perpendicular to        a longitudinal axis (A-A); and a marker link extending between a        first ring and a second ring of the rings, the marker link        including a structure having a hole and a radiopaque material is        contained within the hole; wherein the marker link forms with        the first ring a first ring W crown and with the second ring a        second ring Y crown, wherein a ½ wave length of the first ring        measured from the first ring W crown to an adjacent U crown of        the first ring is greater than a ½ wave length of the second        ring measured from the second ring Y crown to an adjacent U        crown of the second ring.    -   (30) The medical device of (29), in combination with one or more        of, or any combination of items (a) through (g):        -   (a) wherein a length of the marker link is greater than a            length of a link connecting the second ring to a third ring            adjoined with the second ring;        -   (b) wherein the marker link includes a first link portion            extending from the structure to the first ring W crown and a            second link portion extending from the second ring Y crown            to the structure, wherein a width of the first link portion            is greater than a width of the second link portion;        -   (c) wherein a length of the first length portion is less            than a length of the second link portion;        -   (d) wherein the structure includes a first and second holes,            each containing the radiopaque material, wherein the first            and second holes are aligned parallel to the axis A-A;        -   (e) wherein the first ring includes a first, second and            third crest, the first crest corresponding to the first ring            W crown, the second crest is adjacent the first crest and            the third crest is adjacent the second crest, wherein a            second wavelength extending from the second crest to the            third crest is less than a first wavelength extending from            the first crest to the second crest;        -   (f) wherein a flat portion of the first ring W crown is            greater than a flat portion of a third ring W crown of a            third ring adjoined with the second ring, and/or a flat            portion of a fourth W crown of the first ring; and        -   (g) wherein a wavelength of the first ring forming the first            ring W crown is longer than a wavelength of the second ring            forming the second ring Y crown.    -   (31) A medical device, comprising: a thin-walled scaffold having        proximal and distal end portions formed by a network of rings        interconnected by links, wherein each ring has a plurality of        crests, wherein a crest is one of a U crown, Y crown and W        crown, and each ring extends circumferentially in an undulating        fashion along a vertical axis (B-B) perpendicular to a        longitudinal axis (A-A); a marker link extending between a first        ring and a second ring of the rings, the marker link including a        structure having a hole and a radiopaque material is contained        within the hole; wherein the marker link forms with the first        ring a first ring W crown and with the second ring a second ring        Y crown, the first ring W crown corresponding to a first crest;        and wherein a first wave length of the first ring measured from        the first crest to a second crest of the first ring, adjacent        the first crest, is greater than a second wave length of the        first ring measured from the second crest to an adjacent third        crest of the first ring.    -   (32) The medical device of (31), in combination with one or more        of, or any combination of items (a) through (c):        -   (a) wherein the first ring has n crests and n−1 wavelengths            where n is at least 6 and not more than 12, and wherein a            first and second wavelength measured from the first crest            and above and below, respectively, the first crest is            greater than the remaining n−3 wavelengths measured between            the n−1 crests;        -   (b) wherein all of the remaining n−3 wavelengths have the            same length;        -   (c) wherein a length of the marker link is about equal to a            length of a link connecting the second ring to a third ring.    -   (33) A medical device, comprising: a balloon catheter having a        balloon, the balloon having a distal balloon end and a proximal        balloon end; a thin-walled scaffold crimped to the balloon, the        scaffold having proximal and distal end portions formed by a        network of rings interconnected by links, wherein each ring has        a plurality of crests, wherein a crest is one of a U crown, Y        crown and W crown, and each ring extends circumferentially in an        undulating fashion along a vertical axis (B-B) perpendicular to        a longitudinal axis (A-A); a marker link extending between a        first ring and a second ring of the rings, the marker link        including a structure having a hole and a radiopaque material is        contained within the hole; wherein the marker link forms with        the first ring a first ring W crown and with the second ring a        second ring Y crown, the first ring W crown corresponding to a        first crest; wherein a first wave length of the first ring        measured from the first crest to a second crest adjacent the        first crest is greater than a second wave length of the first        ring measured from the second crest to a third crest adjacent        the second crest; wherein the thin-walled scaffold has an outer        diameter of about D-min; and wherein        D-min=(1/π)×[(n×strut_width)+(m×link_width)]+2*t.    -   (34) The medical device of (33), in combination with one or more        of, or any combination of items (a) through (d):        -   (a) wherein a maximum width of the structure measured along            axis B-B is greater than a maximum width of a link extending            between the second ring and a third ring adjoined to the            second ring;        -   (b) wherein the marker link includes a first link portion            extending from the structure to the W crown and a second            link structure extending from the Y crown to the structure,            wherein a width of the first link portion is greater than a            width of the second link portion;        -   (c) wherein a length of the first length portion is less            than a length of the second link portion; and        -   (d) wherein the structure includes a first and second hole            containing the radiopaque material, wherein the first and            second holes are aligned parallel to the axis A-A.    -   (35) A method for making a medical device, comprising: using a        tube comprising poly(L-lactide); forming a thin-walled scaffold        pattern from the tube, the scaffold having proximal and distal        end portions formed by a network of rings interconnected by        links, wherein each ring has a plurality of crests, wherein a        crest is one of a U crown, Y crown and W crown, and each ring        extends circumferentially in an undulating fashion along a        vertical axis (B-B) perpendicular to a longitudinal axis (A-A);        the thin-walled scaffold including at least one marker link        extending between a first ring and an adjoined second ring of        the rings, the marker link including a structure having a hole;        placing a radiopaque material in the marker hole, wherein the        hole has a first size before the material placement and a second        size, greater than the first size after material placement, and        wherein the structure has a width measured along axis B-B; and        crimping the thin-walled scaffold to a balloon catheter; wherein        the thin-walled scaffold is crimped to about a        theoretical-minimum crimped diameter (D-min); and wherein        neither of the crowns adjacent and above and below the structure        overlaps the structure.    -   (36) The medical device of (35), in combination with one or more        of, or any combination of items (a) through (c):        -   (a) wherein the marker link forms with a first ring a first            ring W crown and with the second ring a second ring Y crown,            the first ring W crown corresponding to a first crest, and            wherein a first wave length of the first ring measured from            the first crest to a second crest adjacent the first crest            is greater than a second wave length of the first ring            measured from the second crest to an adjacent third crest;        -   (b) wherein the marker link forms with a first ring the            first ring W crown and with the second ring a second ring Y            crown, a first and second U crown is adjacent and above and            below, respectively, the first ring W crown, a first strut            extends from the first ring W crown to the first U crown and            a second strut extends from the first ring W crown to the            second U crown, wherein a distance between the first U crown            and the second U crown, or a distance between the second            strut to the first strut is greater than or equal to a            maximum width of the marker structure measured along axis            B-B; and        -   (c) wherein the width of the marker structure is greater            than a maximum width of a link connecting the second ring to            an adjacent third ring.    -   (37) A medical device, comprising: a thin-walled scaffold having        proximal and distal end portions formed by a network of rings        interconnected by links of the thin-walled scaffold, wherein        each ring has a plurality of crowns, including U crowns and at        least one of Y crowns and W crowns, each ring extends        circumferentially in an undulating fashion along a vertical axis        (B-B) perpendicular to a longitudinal axis (A-A); the proximal        end portion includes an outermost proximal ring adjoined to a        first proximal ring by first proximal links, and the first        proximal ring is adjoined to a second proximal ring by second        proximal links; the distal end portion includes an outermost        distal ring adjoined to a first distal ring by first distal        links, and the first distal ring is adjoined to a second distal        ring by second distal links; wherein—the first proximal links        include a proximal marker link comprising a proximal hole        containing a radiopaque material, and—the first distal links are        devoid of a link holding the radiopaque material.    -   (38) The medical device of (37), in combination with one or more        of, or any combination of items (a) through (i):        -   (a) wherein the outermost proximal ring is adjoined to the            first proximal ring only by the first proximal links,            wherein two of which extend parallel to axis A-A and have a            constant cross-sectional moment of inertia;        -   (b) wherein the outermost distal ring is adjoined to the            first distal ring only by the first distal links, each of            which are non-linear link struts;        -   (c) wherein the proximal marker link has a first end and a            second end, the first end forming one of a W crown and a Y            crown with the outermost proximal ring and the other of the            W crown and Y crown with the first proximal ring;        -   (d) wherein the first distal ring and second distal ring are            adjoined by a distal marker link;        -   (e) wherein the distal marker link includes a structure that            circumscribes two holes and the first and second distal            rings are adjoined additionally by one or two marker links;        -   (f) wherein the distal marker link has a first end and a            second end, the first end forming one of a W crown and Y            crown with the first distal ring and the other of the W            crown and Y crown with the second distal ring, wherein the W            crown is wider than the Y crown;        -   (g) wherein the proximal marker link further comprises: a            rim substantially circumscribing the hole and defining a            hole wall and a strut rim, wherein a distance between the            wall and rim is D; a radiopaque marker disposed in the hole,            the marker including a head having a flange disposed on the            rim; wherein the flange has a radial length of between ½ D            and less than D; wherein the thin-walled scaffold            thickness (t) is related to a length (L) of the marker            measured between an abluminal and luminal surface of the            marker by 1.1≦(L/t)≦1.8;        -   (h) wherein the distal marker link forms with the first            distal ring one of the W crown and a Y crown with the second            distal ring, wherein a % wave length of the ring having the            W crown, measured from the W crown to a first adjacent crown            is greater than a % wave length of the ring having the Y            crown; and        -   (i) wherein a length of the first proximal links is less            than a length of the first distal links, and/or a length of            the second distal links is less than the first distal links            length.    -   (39) A medical device, comprising: a balloon catheter having a        balloon, the balloon having a distal balloon end and proximal        balloon end; a thin-walled scaffold crimped to the balloon, the        thin-walled scaffold having proximal and distal end portions        formed by a network of rings interconnected by links of the        thin-walled scaffold, wherein each ring has a plurality of        crowns, including U crowns and at least one of Y crowns and W        crowns, each ring extends circumferentially in an undulating        fashion along a vertical axis (B-B) perpendicular to a        longitudinal axis (A-A); the proximal end portion, crimped to        the proximal balloon end, includes an outermost proximal ring        adjoined to a first proximal ring by first proximal links, and        the first proximal ring is adjoined to a second proximal ring by        second proximal links; the distal end portion, crimped the        distal balloon end, includes an outermost distal ring adjoined        to a first distal ring by first distal links, and the first        distal ring is adjoined to a second distal ring by second distal        links; wherein—the first proximal links include a proximal        marker link comprising a proximal hole containing a radiopaque        material,—the first distal links are devoid of a link holding        the radiopaque material, and—the first distal links comprise        non-linear links; wherein the thin-walled scaffold has an outer        diameter of about D-min; and Wherein        D-min=(1/π)×[(n×strut_width)+(m×link_width)]+2*t.    -   (40) The medical device of (39), in combination with one or more        of, or any combination of items (a) through (i):        -   (a) wherein the outermost proximal ring is adjoined to the            first proximal ring only by the first proximal links, each            of which extend parallel to axis A-A and have a constant            cross-sectional moment of inertia;        -   (b) wherein the non-linear links are U-shaped links;        -   (c) wherein the proximal marker link has a first and second            end, the first end forming one of a W crown and Y crown with            the outermost proximal ring and the other of the W crown and            Y crown with the first proximal ring, and wherein the marker            link includes structure circumscribing holes;        -   (d) wherein a first link portion of the proximal marker link            extends from the W-crown to the structure and a second link            portion of the proximal marker link extends from the Y-crown            to the structure, wherein a first link portion length is            greater than a second link portion length;        -   (e) wherein the first link portion length is about equal to            the sum of twice a ring width and a length of a strut            extending between a U crown and a U, Y or W crown of the            ring.        -   (f) wherein the non-linear link has a first and second end,            the first end forming one of a W crown and Y crown with the            outermost proximal ring and the other of a the W crown and Y            crown with the first proximal ring, and wherein the            non-linear link includes a U-shaped structure between the W            crown and Y crown;        -   (g) wherein a first link portion of the proximal U-shaped            link extends from the W-crown to the U-shaped structure and            a second link portion of the proximal marker link extends            from the Y-crown to the structure, wherein a first link            portion length is greater than a second link portion length;        -   (h) wherein the first link portion length is about equal to            the sum of twice a ring width and a length of a strut            extending between a U crown and a U, Y or W crown crowns of            a ring; and        -   (i) wherein the distal marker link has a first and second            end, the first end forming one of a W crown and Y crown with            the first distal ring and the other of the W crown and Y            crown with the second distal ring.    -   (41) A medical device, comprising: a thin-walled scaffold having        proximal and distal end portions formed by a network of rings        interconnected by links of the thin-walled scaffold, wherein        each ring has a plurality of crowns, including U crowns and at        least one of Y crowns and W crowns, each ring extends        circumferentially in an undulating fashion along a vertical axis        (B-B) perpendicular to a longitudinal axis (A-A); the proximal        end portion includes an outermost proximal ring adjoined to a        first proximal ring by first proximal links, and the first        proximal ring is adjoined to a second proximal ring by second        proximal links; the distal end portion includes an outermost        distal ring adjoined to a first distal ring by first distal        links, and the first distal ring is adjoined to a second distal        ring by second distal links; wherein the first proximal links        include a proximal marker link comprising a pair of proximal        holes containing a radiopaque material, wherein the proximal        holes are aligned along axis A-A, and the first distal links        include a distal marker link comprising a pair of distal holes        containing a radiopaque material, wherein the distal holes are        aligned along axis B-B.    -   (42) The medical device of (41), in combination with one or more        of, or any combination of items (a) through (i):        -   (a) wherein the outermost proximal ring is adjoined to the            first proximal ring only by the first proximal links,            wherein two of which extend parallel to axis A-A and have a            constant cross-sectional moment of inertia;        -   (b) wherein the outermost distal ring is adjoined to the            first distal ring only by the first distal marker link and            non-linear link struts;        -   (c) wherein the proximal marker link has a first and second            end, the first end forming one of a W crown and Y crown with            the outermost proximal ring and the other of the W crown and            Y crown with the first proximal ring;        -   (d) wherein a W crown width formed by the first end is            greater than a Y crown width formed by the second end, such            that a wavelength of the ring forming the W crown is longer            than a wavelength of the ring forming the Y crown;        -   (e) wherein the distal marker link has a first and second            end, the first end forming one of a W crown and Y crown with            the outermost distal ring and the other of the W crown and Y            crown with the first distal ring;        -   (f) wherein the distal marker link has a first link portion            extending from the holes to the W crown and a second link            portion extending from the holes to the Y crown, wherein a            length of the first link portion is longer than a length of            the second link portion;        -   (g) wherein the proximal marker link further comprises: a            rim substantially circumscribing the hole and defining a            hole wall and a strut rim, wherein a distance between the            wall and rim is D; a radiopaque marker disposed in the hole,            the marker including a head having a flange disposed on the            rim; wherein the flange has a radial length of between ½ D            and less than D; wherein the thin-walled scaffold            thickness (t) is related to a length (L) of the marker            measured between an abluminal and luminal surface of the            marker by 1.1≦(L/t)≦1.8;        -   (h) wherein the radiopaque material is contained within a            hole and the radiopaque material has a shape of a frustum;            and        -   (i) wherein the hole comprises a first and second opening            located on, respectively, a first and second side of the            marker link, wherein the first opening is larger than the            second opening and the frustum is substantially flush with            the first and second openings.    -   (43) A medical device, comprising: a balloon catheter having a        balloon, the balloon having a distal balloon end and a proximal        balloon end; a thin-walled scaffold crimped to the balloon, the        thin-walled scaffold having proximal and distal end portions        formed by a network of rings interconnected by links of the        thin-walled scaffold, wherein each ring has a plurality of        crowns, including U crowns and at least one of Y crowns and W        crowns, each ring extends circumferentially in an undulating        fashion along a vertical axis (B-B) perpendicular to a        longitudinal axis (A-A); the proximal end portion, crimped to        the proximal balloon end, includes an outermost proximal ring        adjoined to a first proximal ring by first proximal links, and        the first proximal ring is adjoined to a second proximal ring by        second proximal links; the distal end portion, crimped the        distal balloon end, includes an outermost distal ring adjoined        to a first distal ring by first distal links, and the first        distal ring is adjoined to a second distal ring by second distal        links; wherein (1) the first proximal links include a proximal        marker link comprising a structure extending parallel to axis        A-A and containing a radiopaque material, (2) the first distal        links include a distal marker link comprising a structure, and        extending parallel to axis B-B and containing the radiopaque        material; wherein the thin-walled scaffold has an outer diameter        of about D-min; and wherein        D-min=(1/π)×[(n×strut_width)+(m×link_width)]+2*t.    -   (44) The medical device of (43), in combination with one or more        of, or any combination of items (a) through (i):        -   (a) wherein the outermost proximal ring is adjoined to the            first proximal ring only by the first proximal links, each            of which extend parallel to axis A-A and have a constant            cross-sectional moment of inertia;        -   (b) wherein the first distal links include non-linear links;        -   (c) wherein the proximal marker link has a first and second            end, the first end forming one of a W crown and Y crown with            the outermost proximal ring and the other of the W crown and            Y crown with the first proximal ring, and wherein the marker            link includes structure circumscribing holes;        -   (d) wherein a first link portion of the proximal marker link            extends from the W crown to the structure and a second link            portion of the proximal marker link extends from the Y crown            to the structure, wherein a length of the first link portion            is greater than a length of the second link portion.        -   (e) wherein the first link portion length is about equal to            the sum of twice a ring width and a length of a strut            extending between a U crown and a Y, U or W crown of a ring;        -   (f) wherein the first distal links comprise a non-linear            link having a first and second end, the first end forming            one of a W crown and a Y crown with the outermost proximal            ring and the other of the W crown and Y crown with the first            proximal ring, and wherein the non-linear link includes a            U-shaped structure between the W crown and Y crown;        -   (g) wherein a first link portion of the non-linear link            extends from the W crown to the U-shaped structure, and a            second link portion of the non-linear link extends from the            Y crown to the U-shaped structure, wherein a length of the            first link portion length is greater than a length of the            second link portion;        -   (h) wherein the first link portion length is about equal to            the sum of twice a ring width and a length of a strut            extending between a U crown and a Y, U or W crown of a ring;            and        -   (i) wherein the holes of the distal marker link are between            and not overlapping or under-lapping a U-crown adjacent a            W-crown of the outermost distal ring and a U crown adjacent            a Y crown of the first distal ring.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in the presentspecification are herein incorporated by reference to the same extent asif each individual publication or patent application was specificallyand individually indicated to be incorporated by reference. To theextent there are any inconsistent usages of words and/or phrases betweenan incorporated publication or patent and the present specification,these words and/or phrases will have a meaning that is consistent withthe manner in which they are used in the present specification.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a portion of a prior art scaffold. Thescaffold is shown in a crimped state (balloon not shown).

FIG. 2 is a top partial view of a scaffold showing a marker link thathas holes for retaining a radiopaque material and connects adjoiningrings.

FIG. 2A is a reproduction of FIG. 2 showing additional dimensionalcharacteristics and/or feature of link for holding two markers.

FIG. 2B shows an alternative embodiment of a marker link.

FIG. 2C is another reproduction of FIG. 2 with markers attached to thelink.

FIG. 3 shows distal and proximal end portions of a scaffold according toone embodiment. The end portions include the marker link of FIG. 2connecting rings.

FIG. 3A shows section IIIA of the scaffold of FIG. 3.

FIG. 3B shows section IIIB of the scaffold of FIG. 3.

FIG. 3C shows the scaffold of FIG. 3 in a crimped state.

FIG. 3D shows the scaffold of FIG. 3 crimped to a balloon of a ballooncatheter.

FIG. 4 shows end portions of a scaffold according to another embodiment.

The end portions include a link connecting adjoining rings andcontaining a marker. The rings have a W crown formed in-part by themarker link. The W crown is modified to accommodate a marker structure.

FIG. 4A shows section IVA of the scaffold of FIG. 4.

FIG. 4B shows the distal end ring of the scaffold in FIG. 3 with adistal end ring of the scaffold of FIG. 4 in phantom, to showdifferences between the two rings.

FIG. 4C shows section IVC of the scaffold of FIG. 4.

FIG. 4D shows the scaffold of FIG. 4 in a crimped state.

FIG. 5 is a partial view of a scaffold distal end portion according toanother embodiment.

FIG. 6 shows end portions of a scaffold according to another embodiment.The distal end portion is different from the proximal end portion.Non-linear link struts connect the outermost distal ring to an innerring and a marker link is between inner rings at the distal end portion.

FIG. 6A is partial view of the scaffold of FIG. 6 in a crimped state.

FIG. 6B is an image of a catheter distal end in a bent configurationshowing a distal ring of a scaffold flaring or protruding outward fromthe balloon distal end.

FIG. 6C is an image of a catheter distal end in a bent configurationshowing the distal ring of a scaffold according to FIG. 6. The distalend ring no longer flares outward when the catheter is placed inbending.

FIG. 7 shows end portions of a scaffold according to another embodiment.The proximal end portion is different from the distal end portion.Non-linear link struts and a modified marker link connects the outermostdistal ring to an inner ring.

FIG. 7A is a partial view of the scaffold of FIG. 7 in a crimped state.

FIG. 7B is a partial view of the scaffold of FIG. 7 taken at section VIIin FIG. 7.

FIG. 7C is an image of a catheter distal end in a bent configurationshowing the distal ring of a scaffold according to FIG. 7. The distalend ring does not flare outward when the catheter is placed in bending.

FIGS. 8A-8B show a side and top view, respectively, of a markeraccording to another embodiment.

FIG. 9 is a cross-sectional view of a link having a hole and the markerof FIGS. 8A-8B embedded in the hole.

FIG. 10 is a side-cross section of a first die for forming a rivetmarker from a radiopaque bead.

FIG. 11A is a side view of a rivet marker formed using the die of FIG.10.

FIG. 11B is a side cross-section of a scaffold strut with the marker ofFIG. 11A engaged with a hole of the strut and after a forming processdeforms the marker to make upper and lower rims retaining the marker inthe hole.

FIG. 12 is a side-cross section of a second die for forming a rivetmarker from a radiopaque bead.

FIG. 13 is a side view of a rivet marker formed using the die of FIG.12.

FIGS. 14A, 14B and 14C are perspective views depicting aspects of aprocess for deforming a rivet lodged in a scaffold hole to enhanceengagement with the hole to resist dislodgment forces associated withcrimping or balloon expansion.

FIG. 15A is a side cross-sectional view of a deformed rivet marker andscaffold hole following the process described in connection with FIGS.14A-14C.

FIG. 15B is a view of the deformed marker illustrated in FIG. 15A.

FIG. 15C is a side cross-sectional view of the rivet and marker hole ofFIG. 15A following a heating step.

FIGS. 16A through 16C illustrate steps associated with removing a formedrivet marker from a die and placing the rivet marker into the hole ofthe scaffold.

FIGS. 17A and 17B describe a process for crimping a thin-walled scaffoldaccording to the disclosure.

DETAILED DESCRIPTION

In the description like reference numbers appearing in the drawings anddescription designate corresponding or like elements among the differentviews.

For purposes of this disclosure, the following terms and definitionsapply:

The terms “about,” “approximately,” “generally,” or “substantially” mean30%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1.5%, 1%, between 1-2%, 1-3%, 1-5%,or 0.5%-5% less or more than, less than, or more than a stated value, arange or each endpoint of a stated range, or a one-sigma, two-sigma,three-sigma variation from a stated mean or expected value (Gaussiandistribution). For example, d1 about d2 means d1 is 30%, 20%, 15%, 10%,5%, 4%, 3%, 2%, 1.5%, 1%, 0% or between 1-2%, 1-3%, 1-5%, or 0.5%-5%different from d2. If d1 is a mean value, then d2 is about d1 means d2is within a one-sigma, two-sigma, or three-sigma variance or standarddeviation from d1.

It is understood that any numerical value, range, or either rangeendpoint (including, e.g., “approximately none”, “about none”, “aboutall”, etc.) preceded by the word “about,” “approximately,” “generally,”or “substantially” in this disclosure also describes or discloses thesame numerical value, range, or either range endpoint not preceded bythe word “about,” “approximately,” “generally,” or “substantially.”

The “glass transition temperature,” TG, is the temperature at which theamorphous domains of a polymer change from a brittle vitreous state to asolid deformable or ductile state at atmospheric pressure. Thisapplication defines TG and methods to find TG, or TG-low (the lower endof a TG range) for a polymer in the same way as in U.S. application Ser.No. 14/857,635.

A “stent” means a permanent, durable or non-degrading structure, usuallycomprised of a non-degrading metal or metal alloy structure, generallyspeaking, while a “scaffold” means a temporary structure comprising abioresorbable or biodegradable polymer, metal, alloy or combinationthereof and capable of radially supporting a vessel for a limited periodof time, e.g., 3, 6 or 12 months following implantation. It isunderstood, however, that the art sometimes uses the term “stent” whenreferring to either type of structure.

“Inflated diameter” or “expanded diameter” refers to the inner diameteror the outer diameter the scaffold attains when its supporting balloonis inflated to expand the scaffold from its crimped configuration toimplant the scaffold within a vessel. The inflated diameter may refer toa post-dilation balloon diameter which is beyond the nominal balloondiameter, e.g., a 6.5 mm balloon (i.e., a balloon having a 6.5 mmnominal diameter when inflated to a nominal balloon pressure such as 6times atmospheric pressure) has about a 7.4 mm post-dilation diameter,or a 6.0 mm balloon has about a 6.5 mm post-dilation diameter. Thenominal to post dilation ratios for a balloon may range from 1.05 to1.15 (i.e., a post-dilation diameter may be 5% to 15% greater than anominal inflated balloon diameter). The scaffold diameter, afterattaining an inflated diameter by balloon pressure, will to some degreedecrease in diameter due to recoil effects related primarily to, any orall of, the manner in which the scaffold was fabricated and processed,the scaffold material and the scaffold design.

When reference is made to a diameter it shall mean the inner diameter orthe outer diameter, unless stated or implied otherwise given the contextof the description.

When reference is made to a scaffold strut, it also applies to a link orbar arm.

“Post-dilation diameter” (PDD) of a scaffold refers to the innerdiameter of the scaffold after being increased to its expanded diameterand the balloon removed from the patient's vasculature. The PDD accountsfor the effects of recoil. For example, an acute PDD refers to thescaffold diameter that accounts for an acute recoil in the scaffold.

A “before-crimp diameter” means an outer diameter (OD) of a tube fromwhich the scaffold was made (e.g., the scaffold is cut from a dipcoated, injection molded, extruded, radially expanded, die drawn, and/orannealed tube) or the scaffold before it is crimped to a balloon.Similarly, a “crimped diameter” means the OD of the scaffold whencrimped to a balloon. The “before-crimp diameter” can be about 2 to 2.5,2 to 2.3, 2.3, 2, 2.5, 3.0 times greater than the crimped diameter andabout 0.9, 1.0, 1.1, 1.3 and about 1-1.5 times higher than an expandeddiameter, the nominal balloon diameter, or post-dilation diameter.Crimping, for purposes of this disclosure, means a diameter reduction ofa scaffold characterized by a significant plastic deformation, i.e.,more than 10%, or more than 50% of the diameter reduction is attributedto plastic deformation, such as at a crown in the case of a stent orscaffold that has an undulating ring pattern, e.g., FIG. 1. When thescaffold is deployed or expanded by the balloon, the inflated balloonplastically deforms the scaffold from its crimped diameter. Methods forcrimping scaffolds made according to the disclosure are described inUS20130255853.

A material “comprising” or “comprises” poly(L-lactide) or PLLA includes,but is not limited to, a PLLA polymer, a blend or mixture including PLLAand another polymer, and a copolymer of PLLA and another polymer. Thus,a strut comprising PLLA means the strut may be made from a materialincluding any of a PLLA polymer, a blend or mixture including PLLA andanother polymer, and a copolymer of PLLA and another polymer.

Bioresorbable scaffolds comprised of biodegradable polyester polymersare radiolucent. In order to provide for fluoroscopic visualization,radiopaque markers are placed on the scaffold. For example, the scaffolddescribed in U.S. Pat. No. 8,388,673 ('673 patent) has two platinummarkers 206 secured at each end of the scaffold 200, as shown in FIG. 2of the '673 patent.

When reference is made to a direction perpendicular to, or parallelwith/to axis A-A (e.g., as shown in FIG. 3) it will mean perpendicularto, or parallel with/to the axial direction of a scaffold or tube.Similarly, When reference is made to a direction perpendicular to, orparallel with/to axis B-B (e.g., as shown in FIG. 3) it will meanperpendicular to, or parallel with/to the circumferential direction ofthe scaffold or tube. Thus, a sinusoidal ring of a scaffold extendsparallel with/to (in periodic fashion) the circumferential direction orparallel to axis B-B, and perpendicular to axis A-A whereas a link inone embodiment extends parallel to the axial direction or axis A-A ofthe scaffold or tube and perpendicular to the axis B-B.

Wherever the same element numbering is used for more than one drawing itis understood the same description first used for the element in a firstdrawing applies to embodiments described in later drawings, unless notedotherwise.

The dimension of thickness (e.g., wall, strut, ring or link thickness)refers to a dimension measured perpendicular to both of axes A-A andB-B. The dimension of width is measured in the plane of axes A-A andB-B; more specifically, the width is the cross-sectional width from oneside to another side of a contiguous structure; thus, a U-shaped link636 has a constant link width over its length just as link 334 has aconstant link width. Moreover, it is understood that the so-called planeof axes A-A and B-B is technically not a plane since it describessurfaces of a tubular structure having central lumen axis parallel withaxis A-A. Axis B-B therefore may alternatively be thought of as theangular component if the scaffold locations were being described using acylindrical coordinate system (i.e., axis A-A is Z axis and location ofa luminal/abluminal surface of a crown, link, ring, etc. is found by theangular coordinate and radial coordinate constant).

A “thin wall thickness,” “thin-walled scaffold,” “thin-wall” refers to astrut, ring, link, or bar arm made from a polymer comprisingpoly(L-lactide) and having a wall thickness less than 125 microns. Thechallenges faced when working with a thin-walled scaffold are discussedherein, including retaining a marker having the same volume ofradiopaque material

FIG. 2 is a top planar view of a portion of a polymer scaffold, e.g., apolymer scaffold having a pattern of rings interconnected by links.There is a marker link 20 (“link 20”) extending between rings 312 a, 312b in FIG. 2. The link 20 has formed left and right structures or strutportions 21 b, 21 a, respectively, for holding a radiopaque marker. Themarkers are retainable in holes 22 formed by the structures 21 a, 21 b.The surface 22 a corresponds to an abluminal surface of the scaffold.

FIG. 2A is a reproduction of FIG. 2 illustrating additional dimensionalfeatures, specifically characteristic dimensional features D0, D1 andD2. The diameter of the hole 22 is D0. The distance between the adjacentholes 22 is greater than or equal to D1. And the brim width of either orboth holes 22, or distance from the inner wall surface circumscribingeither or both holes 22 to the edge of the link 20 is greater than orequal to D2.

FIG. 2B shows the dimensional features described in connection with FIG.2A for a marker link 720 oriented so that the structures 21 a, 21 b areoffset along axis B-B, as opposed to axis A-A. The marker 720 connectsrings 312 a and 312 b. A scaffold embodying this marker is shown in FIG.7.

FIG. 2C there is shown rivet-type markers 127′/137′ secured in the holes22. The dimensions indicated refer to parameters that may be used toinspect the marker link (after the radiopaque is connected) to evaluateits capacity for resisting forces that tend to dislodge the rivet127′/137′ from the hole 22. These dislodging forces can be produced by apressurized balloon surface or a deformation of nearby scaffoldstructure tending to deform the hole 22, such as when the scaffold iscrimped or balloon expanded. According to one aspect, the rivet headsand/or tails of the rivet 127′/137′ pair may be inspected to determinewhether the minimum distances δ1, δ2, and δ3 (FIG. 2C) are satisfied.The distances δ1, δ2, and δ3 reflect either or both a minimum size of ahead and/or tail of the rivet that was pressed into the hole, whichindicates both that the rivet should hold in the hole 22 (if the head ortail is too small in diameter it cannot resist as well the dislodgingforces) and that excess rivet material will not cause problems such asballoon puncture or vessel irritation when the scaffold is implantedwithin a vessel. According to the embodiments the minimum distance fromthe end of the marker head/tail to the brim of the strut (or link)portion 21 a/21 b, δ2 that is, can be about 10%, 25% and up to 50% ofD2. Above 50% means the head or tail can be too small to hold the rivetin place. For a head/tail equal to, or greater than D2 the head may ordoes extend beyond the brim of the strut/link, which can lead toproblems such as forming a relatively sharp edge than can damage theballoon or irritate adjacent tissue. The minimum distance between themarker heads/tails, δ1 that is, is 0 or up to 25% of the distance D1. Ifthe rims or heads of the markers overlap each other this can exceed themaximum height desired for the strut (about 160 microns). The minimumlength for the head/tail extending to the right or left of the hole 22,δ3 that is, is anything greater than 50% of D2.

Methods for inserting radiopaque markers into holes commonly rely on acylindrical hole to retain the marker. Most of the force of retentioncomes from friction between the walls and the marker material. Markermaterial has been reliably retained in scaffold holes in this mannerwhen the scaffold has a wall thickness of 150 microns and above.However, it becomes far more challenging to hold the marker materialwithin a hole when the wall thickness is reduced to 100 microns or lessthan 100 microns. Although a coating material for carrying a drug canhelp to hold the marker in place, the coatings, such asEverolimus/PDLLA, tends to be quite thin—on the order of 3 microns,which limits it's out of plane shear strength resisting dislodgment ofthe marker from the hole.

There are several desirable properties or capabilities that follow froma reduction in wall thickness for a scaffold strut. The advantages ofusing the reduced wall thickness include a lower profile and hencebetter deliverability, reduced acute thrombogenicity, and potentiallybetter healing. In some embodiments it is desirable to use the same sizemarker for a scaffold having thinner struts, so that there is nodifference, or reduction, in radiopacity between the two scaffold types.Reducing the strut thickness, while keeping the marker hole 22 the samesize can however result in the marker protruding above and/or below thestrut surfaces due to the reduced hole volume. It may be desirable tokeep the abluminal and luminal surfaces 25 a, 25 b of a marker′ flushwith corresponding luminal and abluminal surfaces of the strut, in whichcase the hole 22 diameter (d) may be increased to partially account forthe reduced hole volume resulting from the thinner strut.

Paragraphs [0073] through [0083] of U.S. application Ser. No.14/738,710, which shares a common inventor with this application,describes the factors affecting a scaffold's ability to retain a markerin a hole and the special challenges faced when a wall thickness is lessthan 160 microns, or less than 125 microns. According to someembodiments it has been found that a marker cannot be retained in a holereliably by essentially friction alone when the wall thickness is lessthan 125 microns, i.e., when the scaffold is thin-walled. In a preferredembodiment where the wall thickness is less than 100 microns a markermaterial is retained within a hole using a rivet-shaped marker,discussed briefly above in connection with FIG. 2C and described ingreater detail in connection with FIGS. 8-16.

Following are described embodiments of scaffold patterns suited to meetone of, or a combination of the following objectives:

-   -   (i.) reduced crimped profile for a thin-walled scaffold carrying        a radiopaque marker,    -   (ii.) securing a radiopaque marker in a thin-walled scaffold,    -   (iii.) reducing strain energy buildup in marker-holding        structure when the thin-walled scaffold is being deformed during        crimping, balloon expansion at a target vessel site, or delivery        of the scaffold to a target site, and    -   (iv.) avoiding protruding or flaring end rings at a distal end        of a scaffold for a thin-walled scaffold or scaffold comprising        PLLA and having a wall thickness greater than 125 microns.

It will be appreciated that the above objectives are interrelated andmore than one objective can be addressed by a single change. Forexample, by making a marker link more flexible both of objectives (iii)and (iv) can be met. Scaffolds according to these embodiments may bemade from a thin-walled tube or sheet of material comprisingpoly(L-lactide) (PLLA), which is laser cut from a tubular body toproduce the patterns shown in FIGS. 3-7. Processes to make the tube mayinclude one or more of extrusion, injection molding, solid-phaseprocessing, and biaxial expansion as described in U.S. Ser. No.14/810,344 (62571.1212).

Scaffolds according to the embodiments, e.g., scaffolds 300, 400, 500,600 or 700, are preferably crimped to a balloon catheter, such as theone shown in FIG. 3D. The scaffold may be attached to the balloon tosecure the desired crimped diameter, such as D-min (defined, infra)using any of the crimping processes described in US20130255853;specifically any of the crimping processes and apparatus for crimpingdescribed at paragraphs [0068]-[0073], [0077]-[0099], [0111]-[0126],[0131]-[0146] and FIGS. 1A, 1B, 4A. 4B, 5A, 5B, 8A, and 8B ofUS20130255853.

FIG. 3 shows a partial, planer view of end portions of a scaffoldaccording to one embodiment, or scaffold 300. The left or distal endportion 302 (i.e. the left side of FIG. 3) includes sinusoidal rings 312a, 312 b, and 312 c where ring 312 a is the outermost ring. Ring 312 aand ring 312 b are adjoined by two links 334 and a marker link 20. Ring312 c and ring 312 d are adjoined by three links 334 that extendparallel to axis A-A. The links 334 extend parallel to axis A-A and havea constant cross-sectional moment of inertia across its length, meaninglink 334 has a constant width and thickness and the location of thecentroid or geometric center (or longitudinal axis) of the link iseverywhere parallel with axis A-A. The right or proximal end portion 304(i.e. the right side of FIG. 3) includes sinusoidal rings 312 d, 312 e,and 312 f where ring 312 f is the outermost ring. Ring 312 d and ring312 e are adjoined by three links 334. Ring 312 e and ring 312 f areadjoined by two links 334 and the marker link 20. Thus, scaffold 300 hasa marker link 20 extending between and adjoining the outermost link withthe adjacent, inner ring. The scaffold 300 may have 15, 18 or 20 rings312 interconnected to each other by links 334.

A ring 312, e.g., ring 312 b, is sinusoidal meaning the curvature of thering along axis B-B is best described by a sine wave where thewavelength of the sine wave is equal to the distance between adjacentcrests 311 a of the ring. The ring has a constant width at both crowns307, 309 and 310 and struts 330, which connect a crown to an adjacentcrown.

There are three crown types present in each inner ring 312 b through 312e: U-crown, Y-crown and W-crown. Outermost rings have only the Y-crownor W-crown type, and the U-crown type. A crest or peak 311 a (or troughor valley 311 b) may correspond to a U-crown, Y-crown or W-crown. Forthe outermost ring 312 a there is only a U-crown and W-crown type. Forthe outermost ring 312 f there is only a U-crown and Y-crown type. Amarker link 20 adjoins rings by forming a W-crown with the first ring(e.g., ring 312 e) and a Y-crown with the second ring (e.g. ring 312 f).

A link 334 connects to ring 312 f at a Y-crown 310. A “Y-crown” refersto a crown where the angle extending between a strut 330 of a ring 312and the link 334 is an obtuse angle (greater than 90 degrees). A link334 connects to ring 312 a at a W-crown 309. A “W-crown” refers to acrown where the angle extending between the strut 330 and the link 334is an acute angle (less than 90 degrees). A U-crown 307 is a crown thatdoes not have a link connected to it. Marker link 20 connects to a ringat a W-crown 314 and a Y-crown 316.

For the scaffold 300 there are 6 crests or peaks 311 a and 6 troughs orvalleys 311 b for each ring 312. A crest 311 a is always followed by avalley 311 b. Ring 312 b has 12 crowns: 3 are W-crowns 309, 3 areY-crowns 310 and 6 are U-crowns 307.

FIGS. 3A and 3B show partial, close-up views of the scaffold 300. FIG.3A shows section IIIA of FIG. 3 and FIG. 3B shows section IIIB of FIG.3. The following description, made in respect to FIGS. 3A-3B, appliesthe same for portions 302 and 304 of scaffold 300 with the understandingthat in the case of the link 20 it connects to the outermost ring 312 fat a Y-crown 316 and adjoining ring 312 e at a W-crown 314.

Referring to FIG. 3A, consecutive wavelengths of the outermost ring 312a have lengths L1 and L2, or the distance (along axis B-B) from crown314 to U-crown 307 is L1 and the distance from U-crown 307 to Y-crown309 is L2. The same distances apply for rings 312 b—crown 316 to W-crown309 and W-crown 309 to Y-crown 310 are L1 and L2, respectively. Forscaffold 300 L1=L2=constant for rings 312 a, 312 b. That is, thedistance or wavelength from one crest to another is the same. Also, forscaffold 300 L1+L2 is constant everywhere; that is, for all rings thedistance between a W-crown and Y-crown is the same, as is the distancebetween adjacent crests for the rings 312 a through 312 f. The distanceX in FIG. 3A refers to a half-period or half-length of the sine wave, or½ of L1. The distance X is equal to the distance from the crown 314 tothe adjacent U-crown 307 for crown 312 a. X is the same for ring 312 b.In other embodiments L1 is not equal to L2 and X is different betweenthe outermost ring 312 a and adjoining ring 312 b.

In alternative embodiments, including scaffolds 400, 500 or 700described below, the rings may have zig-zag instead of sinusoidal ringshapes. An example of zig-zag shaped rings is found in FIGS. 5A and 6Aof US20140039604. A zig-zag ring may be described as non-curved strutelements converging at a crown that is shaped to have an inner and outercrown radius. The same description applies, meaning the ring may bedescribed in terms of wavelengths, struts and crowns, except that theshape is not sinusoidal but zig-zag. The term “undulating” refers toboth zig-zag and sinusoidal ring types.

Referring to FIG. 3B, a distance along axis A-A from the peak or crestof the ring 312 a to the peak or the crest of the adjoining ring 312 b,or the length of marker 20 (plus the width t1) is A12. A distance alongaxis A-A from the peak or a crest of the ring 312 b to the peak or thecrest of the adjoining ring 312 c, or length of marker 334 between theserings (plus the width t2) is A23. For scaffold 300 A12=A23. The width ofthe link 20 to the left of marker structure 21 a is tm1 and the width ofthe marker link 20 to the right of structure 21 b is tm2. The width ofthe link 334 is t11. The crowns 307, 310, 309 and 314 and struts 330 ofring 312 a have a constant width t1. The crowns 307, 310, 309 and 314and struts 330 of ring 312 b have a constant width t2. The crowns 307,310, 309 and 314 and struts 330 of ring 312 c have a constant width t3.For scaffold 300 t1 is less than t2 and t2=t3. The dimension B1 and B2refer to a surface of the crowns for rings 312 a and 312 c,respectively, extending parallel to axis B-B or the crown surfaceportion without curvature, i.e., flat. For scaffold 300 B1=B2.

Referring to FIG. 3C there is shown the scaffold 300 having marker 20 ina crimped state. The crimped diameter enforced on scaffold 300 is thetheoretical minimum crimped diameter where struts that converge at thesame crown are in contact with each other when the scaffold is fullycrimped, i.e., when the scaffold is removed from the crimping device, orwhen placed within a restraining sheath soon after crimping. Theequation for the theoretical minimum crimped diameter (D-min) underthese conditions is shown belowD-min=(1/π)×[(n×strut_width)+(m×link_width)]+2*t

Where

-   -   “n” is the number of struts in a ring (12 struts for scaffold        300),    -   “strut_width” is the width of a strut (170 microns for scaffold        300),    -   “m” is the number of links adjoining adjacent rings (3 for        scaffold 300),    -   “link_width” is the width of a link (127 microns for scaffold        300), and    -   “t” is the wall thickness (93 microns for scaffold 300).

Hence, for scaffold 300 D-min=(1/π)×[(12×170)+(3×127)]+2×(93)=957microns.

For adjoined ring pairs 312 a and 312 b at the distal end 302, andadjoined ring pairs 312 e and 312 f at the distal end the marker link 20is wider (along axis B-B) than is a link 334 in order to accommodate themarkers. As a consequence the adjacent struts 330 can often overlap thelink 20 to achieve the same D-min throughout. This condition is depictedin FIG. 3C. Such a state for the crimped scaffold introduces concernsregarding local strength for the rings and link holding the marker. Asshown in FIG. 3C there is an overlap (strut presses against abluminalsurface of marker) or underlap (strut presses against luminal surface ofmarker) by the struts 330 a, 330 b and/or the associated U crownsassociated with these struts. It is preferred to eliminate thisoverlap/underlap when the scaffold is crimped.

Scaffold struts, in particular thin-walled scaffold struts and links,are not designed to twist or carry significant torsion. Twisting occurswhen struts abut and overlap each other. When a scaffold strut has ahigher aspect ratio of width to thickness, there is greater propensityfor the strut to twist when it abuts adjacent structure, e.g., thestructure 21 a of the marker link 20 (a thin walled scaffold has ahigher aspect ratio for the same vessel tissue coverage—strut width—ascompared to a thicker-walled scaffold). As can be appreciated from thedeformed state of FIG. 3C compared with FIG. 3 torsion is introduced inthe ring structure and possibly also the marker link strut. This type ofabnormal deformation can lead to crack propagation or reduced fatiguelife of the ring and/or link 20 at the time of balloon expansion in avessel.

FIG. 3D shows a medical device comprising a balloon catheter and thescaffold 300 crimped to a balloon 15. The distal end 302 of the scaffold300 is nearest the distal end 17 b of the balloon 15 and the proximalend 304 is nearest the balloon proximal end 17 a. The tip of or the mostdistal end 12 of the balloon catheter is shown. A guide wire or mandrel8 extends from the tip 12, exiting from a lumen of the catheter shaft 2.The scaffold crimped to the balloon (according to D-min or other minimumcrimped diameter) can be scaffold 300 or scaffold 400, discussed infra.Scaffolds 500, 600 and 700 may also be used in place of scaffold 300.

As mentioned earlier, when compared to a scaffold that has acomparatively thick wall thickness, such as the scaffold described in US2010/0004735 or the ABSORB GT1 bioresorbable scaffold, the thin-walledscaffold having a similar scaffold pattern was found to exhibit asignificantly higher occurrence rate of strut overlap or underlap(hereinafter MBOL) similar to that shown in FIG. 3C. Higher MBOLoccurrence rates are more likely when the width of the link containingthe markers is made wider to accommodate the same overall volume of themarker material as used in a scaffold having higher wall thicknessstruts. The MBOL can also be higher when a more aggressive crimp isemployed—e.g., D-min crimp profile.

Furthermore, when the same volume marker bead is attached to both thethin-walled and thick-walled scaffolds and the marker is made flush withthe abluminal and luminal surface of the link, the marker bead regionmust adopt a flatter and broader shape, which enforced shape deforms thestructure 21 a and 21 b to increase the propensity for strut overlaps inthe marker bead region, since the marker structure develops a higheraspect ratio to accommodate the marker and/or there can be residualstrain from the marker swaging process, which makes the marker structure21 more susceptible to twisting out of plane. TABLE 1 summarizes thesefindings.

TABLE 1 comparison between scaffold 300 and thicker-walled scaffoldProperty US 2010/0004735 Scaffold 300 Comments/observations Tubingthickness 158 93 Thinner struts may have an (microns) increased tendencyto overlap each other when encountering strut-to-strut sidewall contactduring crimping. 3.0 mm scaffold (before 0.051 (in) 0.041 (in) Moreaggressive crimping crimp size of 3.0 mm) increases the likelihood ofminimum crimp (in) strut-to-strut overlapping Crimped diameter 0.050(in) 0.038 (in) during crimping, or when a restraining sheath is placedover the crimped scaffold. Average marker bead 0.0045 More severeflattening of an sphere radius (in) identical marker bead sphere Markerbead sphere 3.82E−07 3.82E−07 results in a 30% broader volume (in³)theoretical cylinder shape Theoretical marker 0.0088 0.0115 for thethin-walled scaffold, bead cylinder diameter increasing propensity forwhen swaged and flush overlapped struts at marker with strut luminalbead region. surface (in)

Paragraphs [0073] through [0083] of U.S. application Ser. No.14/738,710, which shares a common inventor with this application,describes the factors affecting a scaffold's ability to retain a markerin a hole and the special challenges faced when a wall thickness is lessthan 160 microns, or less than 125 microns. Additionally, the 710application explains how the marker-holding structure must be wider forreduced wall thickness and same radiopaque material volume if the markerwill remain flush—as desired—with the abluminal surface of the strut(therefore, higher aspect ratio and greater tendency for twistingmovement and overlap during crimping). A wider and flatter markerstructure increases the aspect ratio (AR) of the link's width to itswall thickness, which increases the likelihood that the link will twistwhen it comes in contact with an adjacent strut or crown.

In one example the aspect ratio (AR) of the marker link for athin-walled scaffold having a 93 micron wall thickness, compared to anAR for a scaffold having a higher wall thickness of 158 microns, e.g.,as described in US 2010/0004735, and the same volume of marker materialheld by both the 93 micron and 158 micron marker structures, is about4.5 (AR=ts/t=419 micron/93 micron=4.5). For the scaffold having the 158micron all thickness the AR is about 2 (AR=ts/t=322/158). Thus, for thesame volume of marker material and reduction in wall thickness from 158microns to 93 microns the AR increases 2.5 times. Given this significantincrease in the aspect ratio it will be appreciated that the tendencyfor the marker link to twist when it comes in contact with adjacentstruts or crowns during crimping, and/or the struts to overlap/underlapthe marker link can be appreciated.

It is known that during crimping, scaffold bar arms angles reduce andadjacent bar arm struts naturally move toward the link of a w crown. Inthis crimping event, the w crown's “outboard radius” and its centerpoint (usually located outside the link) play a crucial role in guidingthe way the scaffold struts crimp. In fact, the center point of thisoutboard radius tends to act as a pivot point that guides the initialbehavior of the struts and limits the extent of strut motion toward themarker link features. In this second respect, the MBOL occurring betweenstrut and marker link features are closely related to this outboardradius and pivot point location. In the case of the w crown with markerlinks 20 and a thin-walled scaffold design, the center points of the wcrown were initially positioned within the marker structure 21 region.Therefore, during crimping, the strut closure behavior was notkinematically limited, resulting in frequent occurrences ofoverlapping/underlapping with the marker link. To reduce the MBOLoccurrence rate, the center points of the W crown with the markerstructure 21 may be moved to an area outside of the marker structure 21.Hence, during crimping, when the struts of the w crown move toward themarker structure 21, they should avoid pressing into and slipping intoan overlap or underlap state which induces torsion in the w crown and/orlink.

FIG. 4 shows a partial, planar view of end portions of a scaffoldaccording to another embodiment, or scaffold 400. The left or distal endportion 402 (i.e. the left side of FIG. 4) includes sinusoidal rings 412a, 312 b, and 312 c where ring 412 a is the outermost ring. Ring 412 band ring 312 c are adjoined by two links 334 and the marker link 20.Ring 312 c and ring 312 d are adjoined by three links 334 that extendparallel to axis A-A. The right or proximal end portion 404 (i.e. theright side of FIG. 4) includes sinusoidal rings 312 d, 412 b, and 312 fwhere ring 312 f is the outermost ring. Ring 312 d and ring 412 b areadjoined by three links 334. Ring 412 b and ring 312 f are adjoined bytwo links 334 and the marker link 20. Thus, scaffold 400 has a markerlink 20 extending between and adjoining the outermost link with theadjacent ring. The scaffold 400 may have 15, 18 or 20 rings 312interconnected to each other by the links 334.

Scaffold 400 has the same features as described earlier for scaffold300, except as follows. Rings 412 a and 412 b are sinusoidal andadjoined to neighboring rings by W-crowns 414 and Y-crowns 416 (as inthe case of rings 312 a and 312 e), but the ring structure for rings 412a and 412 b near marker 20 is modified to avoid overlapping struts whenthe scaffold is crimped to a minimum theoretical crimp diameter (D-min),as discussed earlier.

Referring to FIGS. 4A and 4C there is shown close-up views of scaffold400 at the sections IVA and IVB from FIG. 4, respectively. To avoid theoverlap discussed earlier the space between struts portions of thew-crown at the marker for ring 412 a and ring 412 b is increased. Thismodification is indicated in the drawings by w-crown 414. The lengthenedcrown (along axis B-B) provides more space between the strut 430 andmarker structure 21 a, 21 b to avoid the overlap (the resulting crimpedshaped with this modification is shown in FIG. 4D). In contrast tow-crowns 309 not associated with the marker link 20, w-crown 414modifies the scaffold structure near the marker 20 in at least one ofways (1), (2) and (3):

-   -   (1) The flat, or non-curved surface portion B1 of the crown is        increased in direction B-B over other w-crown 309 flat surface        parts B2, e.g., an increase of between about 350% to about 400%        for a marker link maximum width (ts) that is about 200% greater        than a non-marker link width (tL).    -   (2) The distance from the w-crown 414 (crest) to the adjacent        u-crown 407 (trough) is increased as compared to the distance        from the y-crown 316 (crest) to the adjacent u-crown 307        (trough) of ring 312 b, and/or for any of rings 312 the distance        from a w-crown 309 (crest) or y-crown 310 (crest) to an adjacent        u-crown 307 (trough). This is indicated in the drawings by        comparing the distance X412 to the distance X312, which measure        the length from the crest center to the trough center of rings        412 and 312, respectively. The distance X412 may be about 15%        greater than X312 for a marker link maximum width (ts) that is        about 200% greater than a non-marker link width (tL).    -   (3) The distance from the crest 414 to the adjacent crest 407 is        greater than the distance from the crest 407 to the crest 409 or        L1 is longer than L2 in FIG. 4A, e.g., L1 is about 10% longer        than L2, and/or L1 is about 5% longer than the distance between        any adjacent crests for rings 312 a, 312 b, 312 d, and 312 f and        for a marker link maximum width (ts) that is about 200% greater        than a non-marker link width (tL).

The features of ring 412 a apply equally to ring 412 b within thevicinity of marker link 20. FIG. 4B shows a view of the portion 302,where ring 412 a is shown in phantom over ring 312 a from scaffold 300.The space added between the marker link 20 and strut 430 is indicated by“increased space” in the drawing. The difference in half-periods of thesinusoidal ring portions (X412, X312) extending between the marker linky-crown and w-crown, respectively, can also be seen in this drawing.Also, the features of ring 412 a are symmetric about the w-crown 414.Therefore, the modifications of at least one of (1), (2) and (3),discussed supra, apply to both sides of the w-crown 414.

According to another aspect of the scaffold 400 in connection with the“increased space” indicated for scaffold 400 to avoid MBOL or overlap,for some embodiments of making the scaffold marker link and connectingrings to avoid overlap, it is advantageous to also factor in deformationof the structure 21 a, 21 b when a marker element, rivet or bead, isswaged into the hole.

FIG. 4D shows a portion of scaffold 400 in a crimped state, where thescaffold has been crimped to D-min. As can be seen here, the added spacebetween the strut-portions 430 a, 430 b of the w-crown 414 at the markerlink 20 results in no overlap or underlap when the scaffold is crimpedto the theoretical minimum crimp diameter, D-m in. Specifically, FIG. 4shows that with the modification to the ring 412 having the W crown 414connection to the marker link 20 the struts and/or U crowns adjacent andabove and below the marker structure are separated by a distance that isgreater than or equal to the maximum width (ts) of the marker structurewhen the scaffold is crimped to D-min. There is no overlap when thescaffold having the ring 412 is crimped to D-min. The marker link iseverywhere between the crowns and struts when the scaffold is crimped toabout D-min.

It has been found that when a thin-walled scaffold similar to scaffold300 was tracked through a simulated calcified and tortuous anatomicmodel, distal end ring distortion was observed due to struts lifting andcatching on obstacles along their path. Additionally, there waspotential for the marker structure 21 and holes 22 to deform/stretchresulting in potential dislodgment of the marker material. To addressthis concern for marker material separation from the thin-walledscaffold, the marker link may be made more flexible in bending bylengthening the link and/or reducing the width of the link portionsconnecting the structure 21 to the adjacent Y or w crown. This changeresults in a more flexible hinge region adjacent to the marker structure21, thereby localizing the deformation to points away from the structure21 to protect the marker hole 22 from significant deformation. Thechange also makes the distal and/or proximal ends of the scaffold moreflexible and conforming to the balloon, thereby reducing the potentialfor strut lifting and catching on obstacles during delivery to a targetsite.

FIG. 5 shows a close up view of another embodiment of a scaffold, orscaffold 500. The view of FIG. 5 is the same as for section IVC of FIG.4 and scaffold 500 has all the features of scaffold 400, except that themarker link adjoining rings 412 a and 312 b and rings 412 b and 312 f ismodified. Marker link 520 differs from marker link 20 in that anadditional link 520 b is added, or the existing link to the right ofmarker structure 21 b (see marker link 20) is lengthened. This added, orlengthened marker link portion results in an increase of the distanceA12 as compared to when marker 20 is used. Also, distance A12 is longerthan distance A23 separating rings not adjoined by a marker link, e.g.,rings 312 b and 312 c in FIG. 5. The same modification—marker link 520replacing marker link 20—is made to the marker link extending betweenrings 412 b and 312 f. Marker link 520 may also replace marker link 20in scaffold 300 (at both proximal and distal ends). In such case, thesame features discussed in respect to scaffold 400 with link 520 alsoapplies to scaffold 300 having link 520.

It was found that when link 20 was replaced by marker link 520 there wasless tendency for the radiopaque material held by the marker structure21 to become dislodged or separate from the scaffold when the scaffoldwas crimped, balloon expanded or tracked through a tortuous vessel. Thereason for the improved retention may be understood by consideration ofthe strain energy distribution over the link when the scaffold isdeformed, or the y-crown 316 of ring 312 b moves relative to the w-crownof ring 412 a.

If crown 316 of ring 312 b moves radially outward or inward relative tocrown 414 of ring 412 a, or the crowns move in opposite directions alongaxis B-B, then the marker link 20 deforms. A significant portion of thestrain energy in the link 20 resulting from this deformation is carriedin the marker structure 21 a, 21 b because the link portions to the leftand right of structure 21 are relatively short and thick (as such, thereis little deformation in this part of the marker link and therefore lessstrain energy carried here). Since the load must be reacted somewherealong the marker link when the ring movement is enforced (i.e.,regardless of the link stiffness the rings will move relative to eachother by a prescribed magnitude because the ring movement occurs by anenforced displacement or overwhelming force, such as by crimper jawsclosing down on the scaffold), the strain energy is mostly carried inthe marker structure 21, which deforms more easily than the short andthick link portions near the crowns. This deformation can change thehole shape that the marker material sits in, thereby resulting in a lossof retention. By lengthening the link portion of the marker 20, oradding link 520 b that is significantly longer than link 520 a, whichrepresents the length for the link portions at left and right sides ofstructure 21 for link 20, the strain energy is instead carried less instructure 21 and more by link 520 b. As a result, there is less tendencyfor the marker material to become dislodged during crimping or bendingof the scaffold because the marker holes 22 retain their shape duringthese loading events. In other words, the deformation of the link occursmostly in the long slender portion 520 b so that the holes 22 can retaintheir shape. Additionally, the link 520 b also increases the flexibilityof the link, thereby enabling the ring 312 b or 312 f to move moreeasily relative to ring 412 a and ring 412 b, respectively. This aspectis advantageous to avoid problems with the distal end ring flaring orprotruding from the balloon when the catheter is navigated about tightvasculature (objective (iv), supra). It is also noted that marker 720,discussed in connection with FIG. 7, similarly addresses objectives (iv)and (iii).

According to one example, the link 520 b forming the y-crown 316 has athickness (tm2) that is about 60% less than the thickness (tm1) of thelink portion 520 a connecting the forming the w-crown 414. Additionally,the length A12 is about 27% longer than the length A23, so as toaccommodate the link 520 with added link portion 520 b.

When a thin-walled scaffold, crimped to a delivery system, was trackedthrough a simulated calcified and tortuous anatomic model, distal endring distortion was observed due to struts catching on obstacles alongtheir path. To understand the possible causes for the strut catching, athin—walled scaffold was crimped to a delivery system of the sameconfiguration and placed in bending similar to what existed in theanatomical model observed under microscope. It was observed that theballoon was under compression on the inner curve of the bend and tensionon the outer curve of the bend. Under tension, the balloon stretched andconformed to the curve. If the w-crown associated with the marker linkhappened to be positioned on the outer curve of the bend, it wouldflare-out (see FIG. 6B) instead of conforming to the underlying curvedballoon material at the distal end 15 a. The w-crown section of thescaffold remains straight since it is stiff due to the marker materialand structure 21.

FIG. 6 shows a partial, planar view of end portions of a scaffoldaccording to another embodiment, or scaffold 600. The left or distal endportion 602 (i.e. the left side of FIG. 6) includes sinusoidal rings 312a, 412 a, and 312 c where ring 312 a is the outermost ring. The right orproximal end portion 604 (i.e. the right side of FIG. 6) includessinusoidal rings 312 d, 412 b, and 312 f where ring 312 f is theoutermost ring. As can be appreciated from FIG. 6 the distal end portion602 is different from the proximal end portion 604. This modification toscaffold 300 or scaffold 400 is made to address occurrences of anon-confirming distal, outermost end ring when the scaffold mounted on aballoon catheter is navigated around a sharp turn in vasculature.

The proximal end portion 604 of scaffold 600 is the same as the proximalend portions 304 or 404 associated with scaffolds 300 and 400,respectively. The distal end portion 602 is modified from distal endportions 302 or 402 in the following ways.

The (distal) marker link 20 of scaffold 600 is located between innerdistal end rings 412 a and 312 c, in contrast to the (proximal) markerlink 20 located between the outermost ring 312 f and inner ring 412 b.This change to the distal end 602 is desirable for at least one ofreasons (a) and (b):

-   -   (a) Improved conformity with distal end balloon: the marker link        20 is stiffer in bending than link 634 or, for that matter, link        334, which can result in separation of the distal outermost ring        from the balloon distal end. When it is not desirable to modify        the marker link structure, or it is not feasible (e.g., because        the structure is needed to provide sufficient surface area to        hold the desired volume of radiopaque material), a significant        reduction in the flexural rigidity of the link connecting the        outermost ring 312 a to interior ring 412 a may be achieved by        moving the marker link 20 to between inner rings. The ability        then to dramatically decrease the flexural rigidity between the        outermost two rings 312 a—objective (iv)—is addressed.    -   (b) Less strain in marker-holding structure: when the scaffold        is navigated about a sharp turn it is the outermost rings that        will experience the highest strain due to the scaffold being        bent. For embodiments of scaffolds where it is not desirable to        make less stiff in bending the outermost ring relative to        adjacent inner ring (e.g., where it is important to avoid a        decrease in radial stiffness for the outermost ring or to avoid        increased spacing between rings for purposes of drug coverage or        vessel support, both of which can occur when the connecting        links are lengthened to make more flexible), by moving the        marker link 20 to a location between inner rings the bending        strain on the link 20 that can cause the marker material to        become dislodged is avoided or mitigated. That is, because the        bending strain in the scaffold (produced when a sharp turn is        made by the catheter) is higher between the outermost ring and        adjacent inner ring than between inner rings, by locating the        link 20 to between inner rings (without a need to change the        marker link structure) the bending strain on the marker        structure 21 is less. Objectives (ii) and (iii) are met.

The scaffold 600 differs also from scaffolds 300 and 400 by the linktype used to connect the outermost ring to the inner ring—that is, thelink 634 connecting ring 312 a to ring 412 a. The outermost distal ring312 a is adjoined with ring 412 a by three non-linear link struts 634that are significantly more flexible in bending than are link struts 334connecting interior rings. This also helps with reason (a) for using ascaffold 600 pattern for the distal end.

A non-linear link strut may take on a variety of shapes, but withcertain restraints such as providing sufficient space for crimping,e.g., D-min crimped profile. The type shown in FIG. 6 has a U-shapedmedial portion 636 connected to the respective y-crown and w-crown by ashort, straight link portion and long, straight link portion,respectively. The link portion connecting the portion 636 to the w-crownis longer than the link portion 632 a connecting to the y-crown in orderto provide sufficient clearance for ring struts during crimping (asexplained below). With this clearance provided the w-crown 309, formedby the link portion 623 a, may be crimped down to D-m in withoutU-shaped portion 636 interfering with struts 330 or struts 330overlapping U-shaped portion 636 in the crimped state.

Referring to FIG. 6A there is shown a crimped side profile for scaffold600. Shown is the link 634 long straight link portion 632 a and shortstraight link portion 623 b with the U-shaped medial portion 636. Thelength A12 (length measured with respect to axis A-A) may exceed thelength A23 by about the length of the U-shaped portion 636, or the sumof the lengths of portions 632 a and 632 b is about equal to A23, lessthe strut width of a ring. In one example, the length A12 is about 40%longer than the length A23.

In other embodiments the U-shaped portion 636 may be replaced by linkshaving a smaller moment of inertia for a region between portions 632 aand 632 b, an S-shaped, notched portion, or narrowed portion replacingU-shaped portion. Examples of these link types are described inUS20140039604 at FIGS. 14B, 14C, 14D, 14E, and 14F, and accompanyingparagraphs [0223]-[0229]. A “non-linear” link strut means any of theselinks.

FIG. 6B is an image showing a deformed distal end of a medical devicecomprising a balloon catheter having a shaft 2 and a scaffold 10 crimpedto the balloon 15. As can be seen in this view, when the catheter isdirected about a sharp turn (as tracked over a guide wire) the balloondistal end and shaft conform to the angle of the turn but the scaffolddistal end 7 does not. More specifically, the outermost ring 5 isflaring or protruding outwards from the distal end. This protrudingstructure 5 can get caught on walls of vasculature. The most pressingconcern with this orientation of the scaffold relative to the balloondistal end is damage that might be caused by the ring 5 catching on thevasculature and damaging the scaffold (due to excessive bending strain).The damage that can occur has been mentioned earlier. First, the markerlink structure can be deformed and result in dislodgment of the markermaterial. Second, the strain can result in fracture of, or crackpropagation within the ring 5.

One solution to this problem may be to make the end rings stiffer inbending, so that the vessel obstruction yields to make space for theflaring or protruding scaffold end. For example, one could make the endrings more thick or increase the number of connecting links between theoutermost ring and inner ring. It is preferred, however, to instead makethe rings less stiff so that the scaffold end will conform more to theballoon distal end. It is also preferred to limit the load put on amarker link, for reasons previously stated. Scaffold 600 (or scaffold700, infra) meets this need.

FIG. 6C is an image of scaffold distal end 602 mounted on the balloon 15distal end 15 a as the catheter makes a similar sharp turn invasculature. As can be seen, by reducing the bending stiffness of thering 312 a relative to the inner ring (ring 312 b) the end ring 312 aconforms to the shape of the balloon distal end 15 a. The end ring 312 adoes not flare or protrude out as in the case of scaffold 5. The links632 act as hinges to accommodate compression and tension that a bendwould exert on the distal end ring when the crimped scaffold is put on abend.

Distal end scaffold conformity with the balloon distal may also beachieved by modifying the marker link structure to become more flexiblein bending. In effect, the w-crown formed by the marker link accordingto the discussion can greatly reduce the stiffness at the w-crownassociated with the marker link 314. The thin-walled scaffold design canthen have the marker link connected to the outermost ring without theflare-out problem discussed earlier.

FIG. 7 shows a partial, planar view of end portions of a scaffoldaccording to another embodiment, or scaffold 700. The left or distal endportion 702 (i.e. the left side of FIG. 7) includes sinusoidal rings 312a, 312 b, and 312 c where ring 312 a is the outermost ring. The right orproximal end portion 704 (i.e. the right side of FIG. 7) includessinusoidal rings 312 d, 412 b, and 312 f where ring 312 f is theoutermost ring. As can be appreciated from FIG. 7 the distal end portionis different from the proximal end portion. This modification toscaffold 300 or scaffold 400 is also made to address occurrences of anon-confirming distal, outermost end ring when the scaffold mounted on aballoon catheter is navigated around a sharp turn in vasculature.

The proximal end portion 704 of scaffold 700 is the same as the proximalend portions 304 or 404 associated with scaffolds 300 and 400,respectively. Moreover, the distal end portion 702 shares some of thecharacteristics of scaffold 600 at the distal end portion 602 except asfollows.

The marker link 720 (FIG. 2B) is located between the outermost ring 312a and inner ring 312 b, as opposed to the marker link 20 or 520 locatedbetween inner links, in the case of scaffold 600. The marker link forscaffold 700 is also different from the marker link of priorembodiments. Marker link 720 has the marker structure 21 orientatedvertically rather than horizontally, as in the case of marker link 20 orlink 520. That is, the marker structure 21 a is offset from the markerstructure 21 b along axis B-B rather than axis A-A. There is a long,straight link portion 732 a connecting the structure 21 at one end andforming the w-crown 314, and a shorter link 732 b at the opposite endforming the y-crown 316.

The outermost ring 312 a for scaffold distal end portion 702 isconnected to the inner ring 312 b by the one marker link 720 and two ofthe non-linear links 634 used in scaffold 600. Adjoined inner rings arenot connected by a marker link 720 or link 634. The link 334 is used.The marker link 720, in contrast to the marker link 20, is more flexiblein bending due to the length of portion 732 a and is favorably locatedbetween the outermost ring and adjacent inner ring to more easily locatethe ends of the scaffold under fluoroscopy. Additionally, one or more ofthe following advantages are also present when marker 720 is used.First, the marker is more flexible so that the outermost ring will moreeasily conform to the balloon when the catheter is navigated about atight turn in the vasculature. In this sense marker 720 has some of thesame advantages as marker 520 (objectives (ii) and (iii)). And no changeis needed to the ring structure to enable a crimping of the ring havingthe w-crown formed by the marker link. The ring 312 a can be crimped toD-min because the structure 21 does not interfere with the ringstructure 21 (objective (i)).

FIGS. 6A and 7A show the crimped states of scaffold 700 near the marker720 and link 634 and lengths between rings A12, A23. As can beappreciated from these views, the portions 732 a and 632 a of the markerand link, respectively, have a length that allows the outer ring 312 ato crimp down to D-min without interference from the U-shaped portion636 or marker structure 21. As can be seen in these views, the structure21 having holes 22 and U-shaped structure 636 are between a U-crownadjacent a W-crown of the ring on the left and a U crown adjacent a Ycrown of the on the right.

Referring to FIG. 7B there is shown a close up view of section VII fromFIG. 7. As indicated here, the respective lengths of portions 732 a and732 b is c1 and c2. The lengths of portions 632 a and 632 b are also c1and c2. Also shown are the lengths A12 and A23 for scaffold 700 (lengthsA12, A23, c1 and c2 also apply to the lengths for portions 632 a and 632b and ring spacing for scaffold 600). The sum of lengths c1 and c2 isequal to A12 less the length of U-shaped portion 636 and width of thecrown. In some embodiments A12 is about 40% greater than A23, c1 isabout 36% longer than c2. The length c1 is about equal to the distancebetween the trough of the adjacent crown and the w-crown formed byportion 732 a or 632 a, less the width of the crown 314 or strut 330,when the scaffold is in the crimped state (see FIGS. 6A-7A). The markerstructure is located to the right of the U-crown adjacent the W-crownformed by the marker link.

FIG. 7C is an image of scaffold distal end 702 mounted on the balloon 15distal end 15 a as the catheter makes a similar sharp turn invasculature. As can be seen, by reducing the bending stiffness of thering 312 a relative to the inner ring (ring 312 b) the end ring 312 aconforms to the shape of the balloon distal end 15 a. The end ring 312 adoes not flare or protrude out as in the case of scaffold 5.

TABLE 2 shows dimensions associated with examples of fabricatedscaffolds corresponding to embodiments of the scaffolds depicted in thefigures (when an entry has “−”, it means the same value as the boximmediately to the left. Thus, the value for tm2 for scaffold 400 is217, and the length B1 for scaffold 500 and scaffold 700 is 374 and 78,respectively).

TABLE 2 FIG. 3/ FIG. 4/ FIG. 5/ FIG. 6/ FIG. 7/ scaffold scaffoldscaffold scaffold scaffold 300 400 500 600 700 (μm) (μm) (μm) (μm) (μm)Ring spacing A12 1110 1110 1300 1426 1427  (crown-to- crown, adjoined bymarker link or non- linear link) Marker link tm1 217 — —  127 127 ornon- tm2 217 —  127 — — linear link ts (max 419 — — — 749 width) c1 n/an/a n/a  596 596 c2 n/a n/a n/a  252 254 Ring spacing A23 1027 — — 11101027  (crown-to- crown, no marker link or non-linear link) Non-marker tL127  127 — — — link Crown length B1 79  374 —  78 — Crown length B2 78 —— — — Ring width t1 178 — —  191 — t2 191 — —  178 191 t3 191 — — — —Wall thickness w 93 — — — — Wavelength L1 1833 1922 1922 n/a n/a(distance L2 1833 1744 1744 n/a n/a between crests) ½ wave length X 9561089 1089 n/a n/a (FIG. 4A: X412 v. X312)

Referring to TABLE 2 as can be appreciated from the above examples, anddiscussed earlier in connection with scaffold 300 compared with scaffold400, 500, 600 and 700; there are changes in the wavelengths, ½wavelengths, marker link thickness, length, and orientation, non-markerlink type and length, ring spacing, and crown width at the marker link,respectively, in response to the needs relating to crimping and/ordelivery of the scaffold through a tortuous artery. These relationshipsapply for a thin-walled scaffold whether in a crimped state or beforecrimped configuration. Thus, when reference is made to a crimpedscaffold, the relationships above also apply. It is also understand thatthe features of scaffold 400 and/or 500 that are different from scaffold300 can be incorporated into scaffolds 600 and 700. Or the features ofscaffold 400 and/or 500 may not be included in the pattern of scaffolds600 and 700.

The following discussion relates primary to meeting objective (ii):securing radiopaque material in a scaffold hole provided by a markerstructure 21 a, 21 b. As mentioned earlier, it has been discovered thatfor thin-walled scaffolds marker material cannot be reliably retained ina marker hole by frictional engagement with walls of a cylindrical hole.To satisfy objective (ii) in preferred embodiments radiopaque materialis secured to any of the scaffolds 300, 400, 500, 600 or 700 by swaginga rivet-like body of the marker material to the marker structure 20, 520or 720, while not impeding any of the other objectives (i), (iii) or(iv). The attaching and securement of the marker, in some embodiments,does not include any added polymer, adhesive or re-shaping of thecylindrical hole (other than the deformation that occurs during theswaging process). In preferred embodiments a drug-polymer coating isapplied after the marker is placed in the hole.

A marker shaped as a rivet is used in place of the spherical marker 25intended for cylindrical hole. FIGS. 8A and 8B show respective side andtop views of the marker 27 shaped as a rivet. The head 28 may includethe abluminal surface 27 a or luminal surface 27 b of the rivet 27. Inthe drawings, the head 28 includes the abluminal surface 27 a. It may bepreferred to the have the head 28 be the luminal surface portion of therivet 27 for assembly purposes, since then the scaffold may be placedover a mandrel and the tail portion of the rivet deformed by a tool(e.g., a pin) applied externally to the scaffold abluminal surface. Therivet 27 has a head diameter d1 and the shank 27 c diameter d2 is aboutequal to the hole 22 diameter. The head 28 has a height of h2, which isabout the amount the head 28 will extend beyond the abluminal surface 22a of the strut portion 21 a. While not desirable, it may be anacceptable protrusion for a head 28 that does not extend more than about25 microns, or from about 5 to 10 microns up to about 25 microns fromthe abluminal surface 22 a, or a head that extends by an amount no morethan about 25% of the strut thickness. The same extent of protrusionbeyond the luminal surface 22 b may be tolerated for the deformed tailof the rivet.

Referring to FIG. 9 there is shown the rivet in the hole 22. Thedeformed tail 27 b′ secures the rivet 27 in the hole 22. The overallheight h1 is preferably not more than about 40% or about 10%-40% greaterthan the strut thickness (t) and the tail height is about the same as,or within 5 to 20 microns in dimension compared to the head height h2.

The rivet 27 may be attached to the hole 22 of the strut portion 21 a byfirst inserting the rivet 27 into the hole 22 from the bore side of thescaffold so that the head 28 rests on the luminal surface 22 b of thestrut portion 21 a. The scaffold is then slipped over a tight fittingmandrel. With the mandrel surface pressed against the head 28 a tool(e.g., a pin) is used to deform the tail 27 b to produce the deformedtail 27 b′ in FIG. 9. In some embodiments, the rivet 27 may be firstinserted into the hole 22 from the abluminal side so that head 28 restson the abluminal surface 22 a of the strut portion 21 a. With the head28 held in place by a tool or flat surface applied against the abluminalsurface, the tail 27 b is deformed by a tool, pin, or mandrel which isinserted into the bore or threaded through the scaffold pattern from anadjacent position on the abluminal surface. In some embodiments therivet 27 may be a solid body (FIG. 8A-8B) or a hollow body, e.g., theshank is a hollow tube and the opening extends through the head 28 ofthe rivet.

In some embodiments a rivet is a hollow or solid cylindrical tube anddevoid of a pre-made head 28. In these embodiments the tube (solid orhollow) may be first fit within the hole then a pinch tool used to formthe head and tail portions of the rivet. According to a preferredembodiment there is a process for making radiopaque markers as rivets,mounting the rivets on a scaffold and a scaffold having such markersmounted thereon. A process for making rivet-shaped markers from beads isdescribed first.

As discussed above head and tail portions of the marker help to hold themarker in place, such as when an external force is applied to the rivetor the link structure is deformed during crimping or balloon expansion,or the scaffold makes a sharp turn in vasculature. In some embodimentshowever a tail portion, e.g., tail 27 b′ of the rivet 27′ in FIG. 9, isnot present. Instead, the rivet's shank portion is deformed to betrapezoidal or frustoconical in shape or to have enlarged end (e.g.,rivet 137′ shown in FIG. 15A). This type of marker has been found toproduce increased resistance to be being pushed out of the hole of astrut or link when the scaffold is subjected to external forces thatdeform the link or strut holding the marker.

It is desirable to choose the appropriate size of the bead for formingthe rivet. According to some embodiments the bead size, or bead volumeto use depends on the strut thickness (t), hole diameter (D2), distancebetween holes (D1) and rim thickness (D2) of the scaffold structurewhere the rivet will be mounted (e.g., the link struts having holes 22in FIG. 2A or 2B). The stock material may be spherical, or cylindrical.Stock made from a radiopaque material can be obtained from commerciallyavailable sources.

According to the disclosure, stock beads are used to make rivet markersfor mounting in scaffold holes 22. In preferred embodiments rivetmarkers are mounted or engaged with scaffold holes of thin-walled strutsor links having a thickness (t) that are preferably less than about 100microns. The steps of a rivet-making process and attachment to ascaffold may be summarized as a six-step process.

STEP 1: select from the stock material a marker bead having a diameteror volume within the desired range, i.e., a diameter or volume suitablefor mounting on a scaffold according to the dimensions D0, D1, D2 and t(FIG. 2B). Selection of the marker bead having the desired diameter orvolume, or removal of a bead too small from the lot, may be accomplishedusing a mesh screen. The lot of beads is sifted over a mesh screen.Beads that do not have the minimum diameter or volume will fall throughopenings in the mesh screen. Alternative methods known in the art mayalso be used to remove unwanted beads or select the right size bead.

STEP 2: deposit the bead selected from Step 1 on a die plate.

STEP 3: cold form the rivet from the bead by pressing the bead into thedie plate. At temperatures close to ambient temperature force the beadthrough the die (e.g., using a plate, mandrel head, pin or tapered ramhead) to thereby re-shape the bead into a rivet defined by the die shapeand volume of the bead relative to the volume of the die receiving thebead.

STEP 4: remove the formed rivets from the die plate. The formed rivets,which can have a total length of about 190-195 microns and diameter ofabout 300-305 microns, are removed using a tool having a vacuum tube.The air pressure is adjusted to grip a rivet at, or release it from thetip. The rivet is removed from the die by placing the opening of thevacuum tube over the head of the rivet, reducing the air pressure withinthe tube to cause the head to adhere to, or become sucked into the tubetip (due to the difference in pressure) and lifting the rivet from thedie.

STEP 5: while the rivet remains attached to the tip of the tube, movethe rivet to a position above the hole of the scaffold, place the rivetinto the hole using the same tool, then increase the air pressure withinthe tool to ambient air pressure. The rivet is released from the tool.

STEP 6: deform the rivet and/or hole to enhance the engagement orresistance to dislodgment of the marker from the hole, e.g., FIGS.14A-14C.

It will be appreciated that according to STEPS 1-6 there is overcome theproblem with the handling of non-spherical beads. For instance, thesteps 1-6 above, wherein the rivet need not be re-orientated after beingformed from a spherical bead, overcomes the problem of orientatedspherical beads so that they can be aligned and placed into holes.

Referring to FIGS. 16A, 16B and 16C there is shown steps associated withtransferring a formed rivet 127′ (or 137′) from a die 200 (or 205) tothe scaffold strut hole 22 using a vacuum tool 350. As can beappreciated, the formed radiopaque marker 127′ is extremely small, i.e.,less than 1 millimeter in its largest dimension, as such the handlingand orientation of the marker 127′ for placement into the hole 22 iscomplicated (in contrast to placement of a sphere into the hole) becauseof the need to orient the shank properly with respect to the hole. Forthis reason the swaging or forging process is combined with placing intothe scaffold hole, by removing the rivet 127′ from the hole 200 with thetool 250, FIG. 16A, maintaining the orientation by keeping the rivet127′ attached to the tool, FIGS. 16B-16C, and then placing the rivet127′ into the hole 22 a, FIG. 16C.

With reference to FIGS. 10 and 11A there is shown a first embodiment ofa die 200 and marker 127 formed using the die 200, respectively,according to the disclosure. The die is a flat plate having a topsurface 201 and a through hole extending from an upper end 201 to alower end. The hole has an upper end diameter dp2 and lower end diameterdp1 less than dp2. The hole 202 is preferably circular throughout,although in other embodiments the hole may be rectangular or hexagonalover the thickness tp, in which case dp1 and dp2 are lengths or extentsacross the hole (as opposed to diameters). And the plate 200 has aheight tp. The taper angle is related to dp2 and dp1 by the expressiontan φ=(½(dp2−dp1)/tp), which in a preferred embodiment 1 is 1 to 5degrees, 5-10 degrees, 3-5, or 2-4 degrees. The shape of die 200produces a frustoconical shank, as depicted in FIG. 18A. A stock bead(not shown) is placed on the upper end of the opening 202 so that thebead sits partially within the hole 202. A flat plate, mandrel or pin(“ram head”) is then pressed into the top of the bead so that the beadis forced into the hole 202. The bead is forced into the hole until theram head is about distance HH from the surface 201. The rivet 127 formedfrom the foregoing forming process has the taper angle φ over all of, ora substantial portion of the shank height SH and the shank shape isfrustoconical. The overall rivet height is HR, the head thickness is HHand the head diameter is HD. In some embodiments the angle φ may besufficiently small so that the shank may be treated as a cylinder, or φis about zero.

With reference to FIGS. 12 and 13A there is shown a second embodiment ofa die 205 and marker 137 formed using the die 205, respectively,according to the disclosure. The die is a flat plate having a topsurface 206 and a hole extending from an upper end 301 to a lower end.The hole has a constant diameter dcb1 throughout. A counter bore isformed on the upper end 206. The counter bore diameter is dcb2. The hole207 is preferably circular throughout, although in other embodiments thehole 207 may be rectangular or hexagonal, in which case dcb1 is a lengthor extent across the hole (as opposed to a diameter). The shape of die200 produces a rivet having a stepped cylindrical shape or cylindricalshank with a head, as depicted in FIG. 13A. A stock bead (not shown) isplaced on the upper end of the opening 207 so that the bead sitspartially within the hole 207. A ram head is then pressed into the topof the bead so that the bead is forced into the hole 207. The bead isforced into the hole until the ram head is about distance HH from thesurface 206. The rivet 137 formed from the foregoing forming processtakes the shape shown in FIG. 13A. The overall rivet height is SH+HH,the head thickness is HH, the shank height is SH and the head diameteris HD.

TABLES 3 and 4, below, provide examples of rivet dimensions for a rivetintended for being secured within a link hole 22 such as shown in FIG.2A. In this example the thickness of the link is 100 microns and thevalues in microns (μm) for D0, D1 and D2 are 241, 64 and 64,respectively.

Values for the die 200 dimensions tp, dp2 and dp1 are 178, 229 and 183.The resulting formed rivet dimensions using die 200 are shown in TABLE3. As can be appreciated from the results, the shank length (or height)is more than 150% of the link thickness and the rivet head diameter (HD)is significantly larger than the hole 22 diameter. The lower portion ofthe shank is relied on to form a tail portion of the rivet. The mean andstandard deviation for HD, SD, and SL are based on the respective “n”samples of rivets measured.

TABLE 3 Rivet formation using tapered plate (FIG. 18A) inches microns nRivet head diameter (HD) mean 0.0123 312 51 from taper plate standarddeviation 0.0015 38 O.D. Rivet head diameter mean 0.0132 335 27 postswage standard deviation 0.0011 28 Shank Diameter (SD) mean 0.0089 22651 standard deviation 0.0004 10 Shank Length (SL) mean 0.0072 183 37standard deviation 0.0009 23

Values for the die 300 dimensions dcb2 and dcb1 are 305 and 203. Theresulting formed rivet dimensions using die 300 are shown in TABLE 3.The mean and standard deviation for HD, SD, HH and SL are based on therespective “n” samples of rivets measured.

TABLE 4 Rivet formation using counter bore plate (FIG. 13A) inchesmicrons n Rivet head diameter (HD) mean 0.012 305 19 from Die standarddeviation 0.0003 10 O.D. Rivet head diameter mean 0.013 330 30 postswage standard deviation 0.0007 18 Rivet head height (HH) mean 0.001 2531 Shank Diameter (SD) standard deviation 0.008 203 31 Shank Length (SL)mean 0.0075 190 24 standard deviation 0.0008 20

In TABLES 3 and 4 “O.D. Rivet head diameter post-swage” refers to theouter diameter of the rivet marker head after the rivet marker ispressed into the scaffold hole.

Discussed now are examples of processes for mounting either of therivets 127, 137 to the scaffold hole 22. According to some embodimentsthe rivet shank is placed into the hole 22 from the abluminal or outerside of the scaffold, so that the head sits on the abluminal surface 22a. The rivet may instead be placed from the luminal side of the hole.The rivet is firmly pressed into the hole so that a maximum portion ofthe shank extends from the luminal or abluminal sides, respectively.

For the rivet 127 after it is placed in the hole 22 the side oppositethe head is subjected to a swaging process. With reference to FIG. 11Bthere is shown in cross-section the deformed rivet 127′ in the hole 22.The rivet 127′ has a head 127 a′ that extends from the surface 22 a byan amount h2. The length h2 may be about 25 microns, between 25 and 50microns or between 5 and 50 microns. The same dimensions apply to a tail127 b′ that extends from the opposite surface of the link (e.g., luminalsurface). The diameter of the head 127 a′ can be larger than the tail,or the tail 127 b′ diameter can be larger than the head 127 a′ diameter.The tail portion is formed from the extended shank length that protrudesfrom the link surface by swaging. The tail 127 b′ is formed by swaging.For example, the rivet 127 is placed in from surface 22 a (abluminalside) so that a significant portion of the shank length, e.g., 50% ofthe strut thickness, extends from the luminal side. A cylindricalmandrel (not shown) is placed through the scaffold's bore. This mandrelhas an outer diameter slightly less than an inner diameter of thescaffold and provides a swaging surface to form the tail 127 b′. Themandrel is rolled back and forth over shank portion extending form theluminal surface. This motion causes the shank material to flatten outaround the hole, thereby producing the tail portion 127 b′. Theresulting rivet 127′ is secured in place, at least in part, by the tailportion 127 b′ resisting forces tending to push the rivet towards theabluminal side of the hole and the head portion 127 a′ resisting forcestending to push the rivet towards the luminal side of the hole 22. Asshown, the deformation of the shank produces the tail 127 b′ having aflange disposed on the surface 22 b. The flange may be circular like thehead and may have a flange radial length greater or less than the radiallength of the flange of the head 127 a′.

With reference to FIGS. 15A and 15B, a stepped mandrel is used inconjunction with a ram head to produce the rivet 137′ from rivet 137.The rivet has a shank 137′ that is reformed from, e.g., agenerally-cylindrical shape when using the die 205, FIG. 12, to theshape shown in FIGS. 15A through 15C. This shank shape may becharacterized by a taper angle θ of magnitude of from between about 5and 15 degrees, 5 to 9 degrees, or about 3 to 8 degrees. The shankaccording to some embodiments of a rivet in the hole 22 is frustoconicalin shape, wherein the shank end opposite, or distal of the head 137 a′,or end 137 b′ is larger or has a larger diameter than the shank portionproximal or nearest the head 137 a′. The deformed shank 22′ may have ashank diameter S2 nearest one of the abluminal and luminal side openingsof the hole 22′ that is larger than the shank diameter S1 nearest theother of the luminal and abluminal side opening, or S2>S1. According tosome embodiments, as shown in FIG. 15A the cylindrical hole 22 is alsodeformed into the hole 22′ that has an opening at surface 22 b largerthan the hole opening at surface 22 a. According to some embodimentsboth the hole 22 and rivet 137 are deformed when the rivet 137 ismounted on the scaffold.

The structure illustrated in FIG. 15A may be made by a second process ofattaching a rivet marker to a scaffold hole 22. In contrast to the firstprocess a tool is not rolled across the surface where the shank tailportion protrudes from the hole opening. Instead, the shank tail end ispushed directly into a non-compliant surface, which can be a surface ofa metal mandrel. The rivet is forced to deform by a compression forcebetween the surface of the mandrel and head of a ram 234, which pushesthe rivet into the mandrel surface. The first process producing thedeformed rivet 127′ by contrast is formed by a combination of rolling ahard surface into the shank and a restraint on the head 127 a, whichholds the rivet head against the surface 22 a while the tail end 127 bis being swaged. Under the second process the force line of action iscompletely along the axis of the rivet, or perpendicular to the rivethead. The result is a flattened or widened shank portion and deformedhole with little or no flange or rim formed from the tail portion of theshank.

The second process is now described in further detail with reference toFIGS. 14A-14C. The scaffold 400 is placed over a stepped mandrel 230.This mandrel has a first outer diameter and a second outer diameter,which is less than the first outer diameter. The scaffold portionholding the marker 137 is placed over the lower diameter portion of themandrel 230. The larger diameter portion of the mandrel 230 holds theadjacent parts of the scaffold. The lower diameter part of the mandrel230 has a surface 230 a and the larger diameter portion has a surface230 b. As shown in FIGS. 14B, 14C the ram 234 pushes with a force F(FIG. 14B) the scaffold portion holding marker 137 into the mandrelsurface 230 a, which causes this scaffold end to deflect a distance “d”towards the surface 230 a (FIG. 14A). After the scaffold reaches thesurface 230 a, the ram 234 continues to push into the scaffold portionholding the marker (by pressing directly against the head 137 a) tocreate the deformed marker 137′ and hole 22′ as shown in FIG. 15A. Thesurface 230 a chosen may be smooth or free of grooves, pitting,depressions or other surface irregularities (other than a surface of acylinder) that would inhibit flow of material during swaging. In apreferred embodiment the mandrel surface is smooth compared to thesurface of the head 234 pressed into the rivet marker 137. That is, thecoefficient of friction (Mu) between the head 234 and surface 137 a′ isgreater than Mu between surface 230 a of mandrel 230 and surface 137 b′.

The shape of the deformed shank 137′ and hole 22′ shown in FIG. 15bproduced higher push-out forces than previously believed (a “push-outforce” means the force needed to dislodge the marker from the hole).Indeed, unexpectedly it was discovered that the deformed rivet 137′ andhole 22′ had a higher resistance to dislodgement than a marker fit intoa link having an over 50% higher thickness, irrespective of the presenceof the head 137 a′. For example, tests for a minimum dislodgment forceneeded to push the rivet 137′ out from the side 22 a of the hole 22′ ofa strut having a 100 micron thickness were higher than the dislodgmentforce needed to push out a marker mounted according to US20070156230(FIGS. 8A, 8B or where the sphere is deformed more into a cylinder whenin the depot, thus increasing the surface-to-surface contact to amaximum) and for a hole of a strut having an about 50%-higher thickness(158 microns vs. 100 microns). As TABLE 4 demonstrates:

TABLE 4 Push-out force Interior hole (gram- Bead surface area force)from volume (thickness × luminal to Scaffold (μm³ × US20070156230diameter × π) abluminal (TABLE 1) Marker process 10⁶) (FIGS. 8A, 8B)(μm² × 10³) side of link A Press sphere into 6.76 wall thickness 158 μm116.2 51.5 hole and hole (n = 8) (US20070156230, diameter 234 μm FIGS.8A, 8B) B FIGS. 14A-14C and 6.76 wall thickness 100 μm 75.7 78.6 usingrivet marker and hole (n = 31) 137 diameter 241 μm

There are higher push-out forces for scaffold B, even though scaffold Ahas more surface area for contact with the marker, thus higherfrictional forces resisting dislodgment. This result indicates that thedeformation that occurs during the swaging process resulting in thedeformed rivet marker and hole of FIG. 15A has a significant effect onthe push-out force (note: the gram-force push-out force reported inTABLE 4 was applied to the luminal side 22 b for scaffold B). Given themore than 50% higher wall thickness Scaffold A should have had a higherdislodgment force (the same bead material, bead volume andpoly(L-lactide) scaffold material for Scaffold A and B). The higherdislodgment force can be explained by the shape of the deformed shankand hole, which essentially produces a lower portion 137 b′ that issignificantly larger than the opening 22 a of the strut 22. Thus, thedislodgment force must be high enough to deform the opening 22 a′ and/orshank portion 137 b′ in order to dislodge the marker from the 22 a sideof hole 22′ (as opposed to only needing to overcome essentially africtional force between the material and walls of the hole).

The shape 137′ in FIG. 15B may be formed by a swaging process thatdeforms the rivet while it sits inside the hole 22. The rivet may havethe shape and/or characteristics of rivet 27, 127 or 137 before swaging.The flow of rivet material transversely (shear flow) during swaging neartail portion 137 b′ causes it to expand out and also yield (enlarge) thestrut hole nearer to opening 22 b′. This produces the trapezoidal-likeor frustoconical shape of the rivet shank and hole. The swaging processof FIGS. 14A-14C applies equal and opposite forces that are aboutco-linear with the axis of symmetry of the rivet (as opposed to arolling motion on one side). If instead a cylinder or sphere (as opposedto a rivet) were placed in the hole 22 and about the same coefficient offriction (COF) existed between the swaging surface 230 a and tail 137 bas the COF between the swaging surface 234 and the head 137 a, butotherwise the same swaging process as in FIGS. 14A-14C, it is believedthat the result would be a more symmetric deformed marker, e.g., asquashed cylinder or barrel-shaped marker depending on the COF, such asthe shape shown in US20070156230. This result can be appreciated fromKajtoch, J Strain in the Upsetting Process, Metallurgy and FoundryEngineering, Vol. 33, 2007, No. 1 (discussing influence of coefficientof friction between ram and ingot on resulting shapes for slendernessratios greater than 2). The shape of the radiopaque material forced intothe hole is also a factor, e.g., a rivet 137 verses a sphere (scaffoldA). The presence of the head on one side results in a shank forming anasymmetric shape about the strut mid-plane axis. It is believed that acombination of the rivet shape and coefficient of friction differencesproduced the favorable result.

In a preferred embodiment a smooth mandrel 230 surface 230 a pressesagainst the surface 137 b, as compared to a more rough surface of thehead 234 that presses against the surface 137 a. In a preferredembodiment the coefficient of friction for the abluminal side wasgreater than 0.17 or Mu>0.17, whereas the coefficient of friction on theluminal side was less than 0.17 or Mu<0.17. As discussed above, theeffect of a difference in the coefficient of friction can be explainedby the restraint on shear or later material flow near the end abuttingthe respective swaging head. If the coefficient of friction issufficiently low then the surface area expands out laterally, as opposedto being held relatively constant. Thus, since Mu is less on the luminalside there is more lateral flow than on the abluminal side. The result,when combined with use the rivet shape, is believed to be thefrustoconical shape as disclosed, e.g., as shown in FIGS. 15A-15B, whichmay be thought of as a shank having a locking angle θ.

There may be a heating step for a scaffold following marker placement.In some embodiments this heating step may correspond to a rejuvenationstep of the scaffold polymer, prior to crimping, to remove aging effectsof the polymer.

Thermal rejuvenation (including thermal treatment of a bioresorbablescaffold above TG, but below melting temperature (Tm) of the polymerscaffold) prior to a crimping process may reverse or remove the physicalageing of a polymeric scaffold, which may reduce crimping damage (e.g.,at the crests of a scaffold) and/or instances of dislodgment of amarker.

According to some embodiments a scaffold is thermally treated,mechanically strained, or solvent treated to induce a rejuvenation orerasure of ageing in a polymer shortly before crimping the scaffold to aballoon and after marker placement. Rejuvenation erases or reverseschanges in physical properties caused by physical ageing by returningthe polymer to a less aged or even an un-aged state. Physical ageingcauses the polymer to move toward a thermodynamic equilibrium state,while rejuvenation moves the material away from thermodynamicequilibrium. Therefore, rejuvenation may modify properties of a polymerin a direction opposite to that caused by physical ageing. For example,rejuvenation may decrease density (increase specific volume) of thepolymer, increase elongation at break of the polymer, decrease modulusof the polymer, increase enthalpy, or any combination thereof.

According to some embodiments, rejuvenation is desired for reversal orerasure of physical ageing of a polymer that was previously processed.Rejuvenation is not however intended to remove, reverse, or erase memoryof previous processing steps. Therefore, rejuvenation also does noteducate or impart memory to a scaffold or tube. Memory may refer totransient polymer chain structure and transient polymer propertiesprovided by previous processing steps. This includes processing stepsthat radially strengthen a tube from which a scaffold is formed byinducing a biaxial orientation of polymer chains in the tube asdescribed herein.

In reference to a marker—scaffold integrity or resistance to dislodgmentduring crimping, it has been found that a heating step can help reduceinstances where crimping causes dislodgment of a marker. According tosome embodiments, any of the foregoing embodiments for a marker heldwithin the scaffold hole 22 can include, after the marker has beenplaced in the hole, a heating step shortly before crimping, e.g., within24 hours of crimping. It has been found that the scaffold is better ableto retain the marker in the hole 22 following heating. A mechanicalstrain, e.g. a limited radial expansion, or thermal rejuvenation (raisethe scaffold temperature above the glass transition temperature (TG) ofthe load-bearing portion of the scaffold polymer for a brief timeperiod) can have a beneficial effect on scaffold structural integrityfollowing crimping and/or after balloon expansion from a crimped state.

In particular, these strain-inducing processes tend to beneficiallyaffect the hole 22 dimensions surrounding the marker when the hole isdeformed in the manner discussed earlier in connection with FIGS.15A-15B.

According to some embodiments the scaffold after marker placement isheated to about 20 degrees, or 30 degrees above the glass transitiontemperature of the polymer for a period of between 10-20 minutes; morepreferably the scaffold load bearing structure (e.g., the portion madefrom a polymer tube or sheet of material) is a polymer comprisingpoly(L-lactide) and its temperature is raised to between about 80 and 85Deg. C for 10-20 minutes following marker placement.

According to some embodiments it has been found that raising thetemperature of the scaffold after marker placement re-shaped portions ofthe hole 22 to improve the fit of the marker in the hole. With referenceto FIG. 15C after the rivet marker 137 is placed in the hole 22according to the second process the hole shape deforms to produce a lipor edge 140 at the end 137 b″, which may produce a higher resistance todislodgment than for a scaffold-marker structure not subsequentlytreated by a rejuvenation step. The surface 140 a of the lip 140interferes more with dislodgment of the marker when a force is directedtowards the end 22 b′.

In accordance with the foregoing objectives of achieving a desired crimpprofile for a thin-walled scaffold there is a method for crimping such ascaffold to a balloon that meets the following needs:

-   -   Structural integrity: avoiding damage to the scaffold's        structural integrity when the scaffold is crimped to the        balloon, or expanded by the balloon.    -   Safe delivery to an implant site: avoiding dislodgement or        separation of the scaffold from the balloon during transit to an        implant site.    -   Uniformity of expansion: avoiding non-uniform expansion of        scaffold rings, which can lead to structural failure and/or        reduced fatigue life.

As previously reported in US20140096357 a scaffold is not as resilientas a stent made from metal, which is highly ductile. The needs thereforefor satisfying all of the above needs are especially for a thin-walledscaffold that can fracture more easily during crimping or balloonexpansion.

FIGS. 17A-17B illustrate steps associated with a crimping process forcrimping to a balloon catheter (FIG. 3D) for the thin-walled scaffolds300, 400, 500, 600 or 700 according to the disclosure. It has been foundthat this crimping process can satisfy all the above needs for ascaffold crimped to D-min. In this example there is a crimping processdescribed for crimping a 3.5 mm scaffold to a 3.0 mm semi-compliantPEBAX balloon. FIG. 17B illustrates in graphical form the crimpingportion of the FIG. 17A flow—a graph of scaffold diameter verses timewith a balloon pressure of between about 20-70 psi (or 1 atm up to thefully or over-inflated balloon pressure) applied throughoutsubstantially all of the crimping process. For example, the balloonpressure is maintained at 70 psi for steps A-G, then the pressure isallowed to decrease (or deflated) to 50 psi (or 1 atm) for the periodG-H. Balloon pressure is removed at point H. No balloon pressure is usedfor steps H-J for purposes of achieving a low crossing profile orcrimping to D-min and avoiding damage to the balloon.

FIG. 17A indicates three possibilities for crimping, depending on need.First, there are two balloons used: Balloon A and Balloon B. balloon Bis used for the pre-crimp step(s) and Balloon A (used with the deliverysystem) is used for the final crimp. Second, there is only one balloonused (Balloon A) for the entire crimp process including the verifyalignment check. In this case, the scaffold inner diameter is largerthan the fully or overinflated Balloon A. As such, during pre-crimpthere may be shifting on the balloon. Third, there is only one balloonused (Balloon A) for the entire crimp process without a verify finalalignment check. In this case, the balloon for the delivery system has afully or overinflated state that is about equal to the inner diameter ofthe scaffold inner diameter.

Stage I: The scaffold supported on the fully inflated balloon of theballoon-catheter is placed within the crimp head. The balloon wheninflated and supporting the scaffold in this state has substantially allfolds removed. In a preferred embodiment the catheter's balloon (i.e.,the balloon used in the final product—a stent delivery system) is usedfor Stage I through Stage II. In other embodiments it may be preferredto use a second, larger balloon for Stage I and II (as explained in moredetail below). The blades of the crimper are heated to raise thescaffold temperature to a crimping temperature. In the preferredembodiments the crimping temperature is between a lower end of the glasstransition temperature for the polymer (TG) and 15 degrees between TG.

After the scaffold reaches the crimping temperature, the iris of thecrimper closes to reduce the scaffold inner diameter (ID) to slightlyless than the outer diameter (OD) of the fully or over inflated balloon(e.g., from 3.45 mm to about 3.05 mm for the PEBAX 3.0 mm semi compliantballoon inflated to a diameter of about 3.2 mm). In this example,Balloon B would be used for the diameter reduction down to the 3.0 mmballoon size, or the Balloon A size (e.g., the 3.0 mm balloon).

Stage II: The crimper jaws are held at the 3.05 mm diameter andmaintained at this diameter for a second dwell period at the crimpingtemperature. After Stage II the scaffold has about 90% of its pre-crimpdiameter.

The foregoing Steps I-II reduce the scaffold diameter down to the sizeof the fully inflated balloon of the stent delivery system (i.e.,Balloon A). Since at the time of the initial alignment check (before anycrimping) the scaffold inner diameter was larger than the balloon fullyinflated diameter (e.g. the scaffold diameter is about 109%-116% of thefully inflated balloon diameter for a balloon with diameters of 3.0 mmto 3.2 mm, respectively) there is a possibility that the scaffold shiftslongitudinally (relative to the balloon) while being crimped down to theballoon size. Given this possibility, the scaffold is removed from thecrimper and its alignment on the balloon is checked relative to proximaland distal balloon markers.

“Verify final alignment” step: When the scaffold requires adjustment onthe balloon, a technician makes manual adjustments to move the scaffoldinto position. It has been found difficult, however, to make these minoradjustments while the scaffold rests on the fully inflated balloon andhas an inner diameter slightly less than the balloon's outer diameter.To address this need, the balloon pressure is slightly decreased, or theballoon temporarily deflated so that the re-alignment may be done moreeasily. When the scaffold is properly re-aligned between the balloonmarkers, the scaffold and fully inflated balloon are placed back intothe crimper. With the scaffold inner diameter and balloon sizes nowabout equal the final crimping of the scaffold to the catheter's ballooncan commence. To ensure no further longitudinal movement of the scaffoldrelative to the balloon, it is preferred to have the scaffold diameterbe slightly less than the balloon fully inflated diameter prior to thestart of Stage III. As noted above, where two balloons are used, BalloonB is replaced with Balloon A, alignment is done with respect to BalloonA and the scaffold is crimped down to the final diameter on Balloon B.

Stage III: The scaffold and balloon are returned to the crimper. Thejaws are closed to a diameter about the same as, or slightly larger thanin Stage II (to account for recoil occurring during the alignmentcheck). The crimper jaws are held at this diameter for a third dwelltime, which may be the time needed for the scaffold to return to thecrimping temperature.

The iris diameter is then reduced to an ID corresponding to about, orslightly less than the OD for the balloon if the balloon were notpressurized and had randomly distributed folds. That is, the scaffold iscrimped down to the approximate OD for the balloon if it werepressurized then deflated so that substantially all pre-made folds arereplaced by random folds. For example, the iris diameter is reduced downto about 1.78 mm for the 3.5 mm scaffold. After this diameter reductionthe scaffold OD is about 60% of its diameter at Stage III and about 50%of its starting, or pre-crimp OD.

Stage IV: After the scaffold OD is reduced to about 50% of its startingdiameter, the crimper jaws are held at this diameter for a third dwelltime. In a preferred embodiment balloon pressure is slightly decreasedduring this dwell. For example, for the 3.0 mm semi-compliant PEBAXballoon the pressure is decreased from 70 psi to 50 psi during the StageIV dwell. This decrease is preferred to achieve a lower crossing profileand/or to protect balloon material from overstretch.

Following the Stage IV dwell period, the balloon is deflated or allowedto return to atmospheric pressure and the iris of the crimper is reduceddown to a final crimp OD, e.g., 1.01 mm or about 30% of its pre-crimpOD. This balloon deflation may occur by opening the valve supplying thepressurized gas to the balloon while, or just before the iris diameteris reduced to the final crimp diameter.

The crimper jaws are then held at the final crimp diameter for about a170 second dwell period, or between 100 and 200 seconds with thecrimping temperature maintained (i.e., scaffold temperature beingbetween 15 degrees below TG and about TG) or without the crimpingtemperature being maintained. This final dwell period is intended toreduce the amount of scaffold recoil when the crimped scaffold isremoved from the crimper. Immediately following the 170 second dwell thescaffold is removed and a retaining sheath is placed over the scaffoldto further aid in reducing recoil. A leak test may be done after thefinal stage crimping.

It may be necessary to provide auxiliary pressure sources for a balloonin order to maintain a relatively constant pressure throughout thediameter reduction and dwell periods (as illustrated in the aboveexample). Indeed, in one embodiment it was found that during diameterreduction there was a pressure drop in the balloon. To address thispressure drop, a secondary pressure source was used to maintain the samepressure during diameter reductions as during dwell periods.

The foregoing example of a preferred crimping process, which selectivelypressurizes the balloon throughout the crimping steps, is expected toprovide three benefits while minimizing any possible overstretching ofthe balloon. The first benefit is increased scaffold-balloon retention.By maintaining relatively high pressure in the balloon through most ofthe crimping steps, more balloon material should become disposed betweenstruts of the scaffold since balloon material is being pressed more intothe scaffold, than the case when crimping is done without balloonpressurization, or only after the scaffold is substantially reduced indiameter. Additionally, it is expected that by substantially removingfolds before any diameter reduction, the balloon material becomes morecompliant. As such, more balloon material is able extend between struts,rather than being pressed between the scaffold and catheter shaft whenthe scaffold is being crimped.

The second benefit of balloon pressurization is more uniform expansionof the crimped scaffold when the balloon is expanded. When the balloonis inflated from the beginning, before any crimping takes place and whenthere is the greatest space available for the balloon to unfold withinthe mounted scaffold, balloon material become more uniformly disposedabout the circumference of the catheter shaft after crimping. In apreferred embodiment the balloon is fully inflated and held at thisinflated state for at least 10 seconds before any crimping to ensure allpre-made folds are removed. If the balloon is only partially expanded,as in the case where the balloon is inflated after the scaffold has beenpartially crimped (thereby leaving less space available for the balloonto fully unfold), fold lines or balloon memory not removed by balloonpressure, it is believed that the presence of folds or partial foldscauses balloon material to shift or displace during crimping, therebyresulting in a more non-uniform distribution of balloon material aboutthe circumference of the catheter shaft after crimping.

The third benefit is avoidance of out of plane twisting or overlappingscaffold struts, which can result in loss of strength, cracks orfracture in struts. As discussed earlier, support of the scaffold withincrimper with an inflated balloon is believed to counteract or minimizeany tendency for struts to move out of alignment.

The foregoing benefits may be achieved without risk that balloonmaterial will be excessively stretched during the crimping process whenballoon pressure is selectively controlled. Referring to FIG. 3B, thepressure range provided is 20-70 psi. The upper end of this pressurerange forms the fully inflated balloon in the case of the balloon usedin the example and may be maintained for the first three stages. Balloonpressure reduction to 50 and 20 psi for Stage IV follows. It was foundthrough several tests that maintaining a constant, and consistent fullyinflated balloon pressure up until the beginning of stage IV or afterthe crimped scaffold had reached about ½ of the original scaffolddiameter, followed by a slight decrease in pressure, provided a goodbalance of stent retention, uniform expansion, low crossing profile,uniform crimping and avoidance of damage to balloon material.

As noted earlier, there are three possibilities for crimping: use twoballoons—Balloon A and Balloon B. Balloon B is used for the pre-crimpstep (a) and Balloon A (used with the delivery system) is used for thefinal crimp. Second, there is only one balloon used (Balloon A) for theentire crimp process including the verify alignment check. In this case,the scaffold inner diameter is larger than the fully or overinflatedBalloon A. As such, during pre-crimp there may be shifting on theballoon. Third, there is only one balloon used (Balloon A) for theentire crimp process without a verify final alignment check. In thiscase, the balloon for the delivery system has a sully or overinflatedstate that is about equal to the inner diameter of the scaffold innerdiameter. These different embodiments are described further, below.

In some embodiments a process is described by the example in FIGS.17A-17B and as described above, with the following exception. Twoballoons are used—a sacrificial or secondary balloon (Balloon B) inaddition to the catheter's balloon (Balloon A)—as opposed to onlyBalloon A as in the above example of a preferred embodiment. Balloon Bis a balloon that has a larger nominally inflated balloon diameter thanBalloon A, or is capable of being over inflated to a larger diameterthan Balloon A. Balloon B is used for Stages I and II. Balloon B isselected to have a fully inflated diameter that is the same as, orslightly larger than the original inner diameter of the scaffold. Oneadvantage of this alternative embodiment is that the scaffold issupported by a balloon throughout the crimping process (as opposed tothe above example where Balloon A can provide little or no radialsupport for the scaffold since there is a gap at Stage I). After StageII, the scaffold is removed from the crimper and Balloon B is replacedby Balloon A. Thereafter, the crimping process continues as describedearlier.

The above description of illustrated embodiments of the invention,including what is described in the Abstract, is not intended to beexhaustive or to limit the invention to the precise forms disclosed.While specific embodiments of, and examples for, the invention aredescribed herein for illustrative purposes, various modifications arepossible within the scope of the invention, as those skilled in therelevant art will recognize.

These modifications can be made to the invention in light of the abovedetailed description. The terms used in claims should not be construedto limit the invention to the specific embodiments disclosed in thespecification.

What is claimed is:
 1. A medical device, comprising: a thin-walledscaffold having proximal and distal end portions formed by a network ofrings interconnected by links, wherein each ring has a plurality ofcrowns, including U crowns and at least one of Y crowns and W crowns,each ring extends circumferentially in an undulating fashion along avertical axis (B-B) perpendicular to a longitudinal axis (A-A); theproximal end portion includes an outermost proximal ring adjoined to afirst proximal ring by first proximal links, and the first proximal ringis adjoined to a second proximal ring by second proximal links; thedistal end portion includes an outermost distal ring adjoined to a firstdistal ring by first distal links, and the first distal ring is adjoinedto a second distal ring by second distal links; wherein (1) the firstproximal links include a proximal marker link comprising a pair ofproximal holes containing a radiopaque material, wherein the proximalholes are aligned along axis A-A, and (2) the first distal links includea distal marker link comprising a pair of distal holes containing aradiopaque material, wherein the distal holes are aligned along axisB-B.
 2. The medical device of claim 1, wherein the outermost proximalring is adjoined to the first proximal ring by only the first proximallinks, and a first proximal link extends parallel to axis A-A and has aconstant cross-sectional moment of inertia.
 3. The medical device ofclaim 2, wherein the outermost distal ring is adjoined to the firstdistal ring by only the first distal marker link and non-linear linkstruts.
 4. The medical device of claim 1, wherein the proximal markerlink has a first and second end, the first end forming one of a W crownand Y crown with the outermost proximal ring and the other of the Wcrown and Y crown with the first proximal ring.
 5. The medical device ofclaim 4, wherein a W crown width formed by the first end is greater thana Y crown width formed by the second end, such that a wavelength of thering forming the W crown is longer than a wavelength of the ring formingthe Y crown.
 6. The medical device of claim 1, wherein the distal markerlink has a first and second end, the first end forming one of a W crownand Y crown with the outermost distal ring and the other of the W crownand Y crown with the first distal ring.
 7. The medical device of claim6, wherein the distal marker link has a first link portion extendingfrom the holes to the W crown and a second link portion extending fromthe holes to the Y crown, wherein a length of the first link portion islonger than a length of the second link portion.
 8. The medical deviceof claim 1, wherein the proximal marker link further comprises: a rimsubstantially circumscribing the hole and defining a hole wall and astrut rim, wherein a distance between the wall and rim is D; aradiopaque marker disposed in the hole, the marker including a headhaving a flange disposed on the rim; wherein the flange has a radiallength of between ½ D and less than D; wherein the thin-walled scaffoldthickness (t) is related to a length (L) of the marker measured betweenan abluminal and luminal surface of the marker by 1.1≦(L/t)≦1.8.
 9. Themedical device of claim 1, wherein the radiopaque material is containedwithin a hole and the radiopaque material has a shape of a frustum. 10.The medical device of claim 9, wherein the hole comprises a first andsecond opening located on, respectively, a first and second side of thelink, wherein the first opening is larger than the second opening andthe frustum is substantially flush with the first and second openings.11. A medical device, comprising: a balloon catheter having a balloon,the balloon having a distal balloon end and a proximal balloon end; athin-walled scaffold crimped to the balloon, the thin-walled scaffoldhaving proximal and distal end portions formed by a network of ringsinterconnected by links, wherein each ring has a plurality of crowns,including U crowns and at least one of Y crowns and W crowns, each ringextends circumferentially in an undulating fashion along a vertical axis(B-B) perpendicular to a longitudinal axis (A-A); the proximal endportion, crimped to the proximal balloon end, includes an outermostproximal ring adjoined to a first proximal ring by first proximal links,and the first proximal ring is adjoined to a second proximal ring bysecond proximal links; the distal end portion, crimped the distalballoon end, includes an outermost distal ring adjoined to a firstdistal ring by first distal links, and the first distal ring is adjoinedto a second distal ring by second distal links; wherein (1) the firstproximal links include a proximal marker link comprising a structureextending parallel to axis A-A and containing a radiopaque material, (2)the first distal links include a distal marker link comprising astructure, and extending parallel to axis B-B and containing theradiopaque material; wherein the thin-walled scaffold has an outerdiameter of about D-min; and whereinD-min=(1/π)×[(n×strut_width)+(m×link_width)]+2*t, “n” is the number ofstruts in a ring, “strut_width” is the width of a strut, “m” is thenumber of links adjoining adjacent rings, “link width” is the width of alink, and “t” is the wall thickness.
 12. The medical device of claim 11,wherein the outermost proximal ring is adjoined to the first proximalring only by the first proximal links, each of which extend parallel toaxis A-A and have a constant cross-sectional moment of inertia.
 13. Themedical device of claim 12, wherein the first distal links includenon-linear links.
 14. The medical device of claim 11, wherein theproximal marker link has a first and second end, the first end formingone of a W crown and Y crown with the outermost proximal ring and theother of the W crown and Y crown with the first proximal ring, andwherein the marker link includes structure circumscribing holes.
 15. Themedical device of claim 14, wherein a first link portion of the proximalmarker link extends from the W crown to the structure, and a second linkportion of the proximal marker link extends from the Y crown to thestructure, wherein a length of the first link portion is greater than alength of the second link portion.
 16. The medical device of claim 15,wherein the first link portion length is about equal to the sum of twicea ring width and a length of a strut extending between crowns of a ring.17. The medical device of claim 11, wherein the first distal linkscomprise a non-linear link having a first and second end, the first endforming one of a W crown and a Y crown with the outermost proximal ringand the other of the W crown and Y crown with the first proximal ring,and wherein the non-linear link includes a U-shaped structure betweenthe W crown and Y crown.
 18. The medical device of claim 17, wherein afirst link portion of the non-linear link extends from the W crown tothe U-shaped structure, and a second link portion of the non-linear linkextends from the Y crown to the U-shaped structure, wherein a length ofthe first link portion length is greater than a length of the secondlink portion.
 19. The medical device of claim 18, wherein the first linkportion length is about equal to the sum of twice a ring width and alength of a strut extending between crowns of a ring.
 20. The medicaldevice of claim 11, wherein the holes of the distal marker link arebetween a U-crown adjacent a W-crown of the outermost distal ring and aU crown adjacent a Y crown of the first distal ring.